References on the Administration of Antibiotics Using
ALZET^® Osmotic Pumps

1. Actinomycin D

P1379 Kanje,M., Lundborg,G., Edstrom,A. A new method for studies of the effects of locally applied drugs on peripheral nerve regeneration in vivo. Brain Research 1988; 439(--):116-121. >>> Actinomycin D; Cycloheximide; Mitomycin C; Vinblastine; Ringer's solution; CSF/CNS (sciatic nerve); rat; 2001; 2002; 3, 4, 6 days; mp connected to silicone cuff; functionality of mp verified in vivo with dye; tissue perfusion.

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2. Amikacin

P8296 Sykes,J.M., Ramsay,E.C., Schumacher,J., Daniel,G.B., Cox,S., Papich,M. Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata). JOURNAL OF ZOO AND WILDLIFE MEDICINE 2006; 37(-3-):373-380. >>> Amikacin; Saline, sterile; Intracoelomic; Snake (corn); 1002; ; Functionality of mp verified by plasma levels; comparison of IM injections vs. mp; half-life (p. 376) 44-45 hours; animal info (male, female, 115-328 grams); "…pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes." (p. 373); temperatures between 27.2-27.7 C.

P4730 Duan,M., Agerman,K, Ernfors,P., Canlon,B. Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity.. PNAS 2000; 97(-13-):7597-7602. >>> NT-3; Amikacin;; Perilymph, artificial;; Ear (cochlea);; guinea-pig;; 2ML2;; 15 days;; Antibiotic; Controls received mp w/ vehicle; tissue perfusion (scala tympani); Amikacin is an aminoglycoside antibiotic; Group 1 received amikacin, Group 2 received vehicle, Group 3 received amikacin and NT-3; All treatment groups received drug for 1 day, followed by 2 weeks perilymph;.

P4403 Ernfors,P., Duan,M.L., ElShamy,W.M., Canlon,B. Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3. Nature Medicine 1996/4; 2(-4-):463-467. >>> Amikacin; NT-3;; Perilymph, artificial;; Ear (cochlea);; guinea-pig;; 2ML2;; 2 weeks;; Antibiotic; controls received mp with vehicle; tissue perfusion (scala tympani); peptides; Lynch coil used, agents or vehicle given in different sequential combinations;.

P0601 Perry,C.R., Rice,S., Ritterbusch,J.K., Burdge,R.E. Local administration of antibiotics with an implantable osmotic pump. Clin.Orthop. 1985; 192(--):284-290. >>> Amikacin; Gentamicin; bone; rabbit; 2001; 2ML1; 6 days; Antibiotic; comparison of im injection vs. mp infusion; no stress p. 289 - no tissue reaction; antibiotic; tissue perfusion.

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3. Bleomycin

P8144 Gu,L., Zhu,Y.J., Yang,X., Guo,Z.J., Xu,W.B., Tian,X.L. Effect of TGF-beta/Smad signaling pathway on lung myofibroblast differentiation. Acta Pharmacologica Sinica 2007; 28(-3-):382-391. >>> Bleomycin; Saline; SC; Mice; 1007D; 7 days; Controls received mp w/ vehicle; functionality of mp verified by examination; no stress (see p.384); animal info (Smad 3 -/- or wt, 8-10 wks old, 17g. 27g.).

P7882 Inayama,M., Nishioka,Y., Azuma,M., Muto,S., Aono,Y., Makino,H., Tani,K., Uehara,H., Izumi,K., Itai,A., Sone,S. A novel I kappa B kinase-beta inhibitor ameliorates bleomycin-induced pulmonary fibrosis in mice. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2006; 173(-9-):1016-1022. >>> Bleomycin; SC; Mice; 2001; ; Controls received mp w/ saline; animal info (female, C57BL/6, 8 wk old, 18g.).

P7713 Fujimoto,H., Gabazza,E.C., Taguchi,O., Nishii,Y., Nakahara,H., Bruno,N.E., Alessandro-Gabazza,C.N., Kasper,M., Yano,Y., Nagashima,M., Morser,J., Broze,G.J., Suzuki,K., Adachi,Y. Thrombin-activatable fibrinolysis inhibitor deficiency attenuates bleomycin-induced lung fibrosis. American Journal of Pathology 2006; 168(-4-):1086-1096. >>> Bleomycin; Saline; SC; Mice; 7 days; Controls received mp w/ vehicle; animal info (female, C57BL/6, 18-22 g); pulmonary.

P7407 Aono,Y., Nishioka,Y., Inayama,M., Ugai,M., Kishi,J., Uehara,H., Izumi,K., Sone,S. Imatinib as a novel antifibrotic agent in bleomycin-induced pulmonary fibrosis in mice. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 2005; 171(-11-):1279-1285. >>> Bleomycin; Saline; SC; Mice; 2001; 28 days; Controls received mp w/ vehicle; pumps replaced every 7 days; peptides; lung fibrosis induced by bleomycin.

P6658 Haston,C.K., Wang,M., Dejournett,R.E., Zhou,X.H., Ni,D., Gu,X.J., King,T.M., Weil,M.M., Newman,R.A., Amos,C.I., Travis,E.L. Bleomycin hydrolase and a genetic locus within the MHC affect risk for pulmonary fibrosis in mice. Human Molecular Genetics 2002; 11(-16-):1855-1863. >>> Bleomycin; SC; Mice; ; Minipump usage mentioned on p. 1860; pump model not listed.

P5586 Li,J., Ortiz,L.A., Hoyle,G.W. Lung pathology in platelet-derived growth factor transgenic mice: Effects of genetic background and fibrogenic agents. Experimental Lung Research 2002; 28(-6-):507-522. >>> Bleomycin; SC; mice; 7 days; controls received mp with saline.

P5168 Zhao,J.S., Shi,W., Wang,Y.L., Chen,H., Bringas,P.Jr, Datto,M.B., Frederick,J.P., Wang,X.F., Warburton,D. Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 2002; 282(--):L585-L593. >>> Bleomycin sulfate; Saline; SC; Mice (knockout); 1007D; 7 days; Antibiotic; Controls received mp w/ vehicle; functionality verified by residual volume.

R0180 Urquhart,J. Controlled drug delivery: therapeutic and pharmacological aspects. J.Intern.Med. 2000; 248(--):357-376. >>> Bleomycin; ; review of controlled drug delivery systems: historical overview, applications, benefits.

P4668 Schwartz,D.R, Homanics,G.E, Hoyt,D.G., Klein,E, Abernethy,J, Lazo,J.S. The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance.. Proc.Natl.Acad.Sci. 1999; 96(--):4680-4685. >>> Bleomycin;; Saline;; SC;; rat;; 2001;; 7 days;; Antibiotic; Controls received mp w/ vehicle; cancer; peptides; bleomycin is a glycopeptide anticancer agent;.

P3397 Haston,C.K., Amos,C.I., King,T.M., Travis,E.L. Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse. Cancer Res. 1996; 56(--):2596-2601. >>> Bleomycin; Saline; SC; mice; 2001; no duration posted; Antibiotic; controls received mp w/saline; cancer; toxicology.

P2643 Bokemeyer,C., Ludwig,E., Reile,D., Harstrick,A., Poliwoda,H., Schmoll,H.J. Antitumor activity and toxicity of continuous infusion versus bolus administration of bleomycin in two heterotransplanted human testicular cancer cell lines. Oncology Reports 1995; 2(--):161-165. >>> Bleomycin; SC; mice (nude); 7 days; Antibiotic; comparison of bolus ip injections vs. mp; cancer; toxicology; ". . .bolus application of bleomycin is at least as active as continuous infusion. . .".

P2007 Rodgers,K.E., Girgis,W., diZerega,G.S. Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal administration of antineoplastic agents. Cancer Chemother.Pharmacol. 1992; 29(--):248-251. >>> Doxorubicin HCl; Mitoxantrone; Tolmetin sodium; Bleomycin; Cisplatin; Methotrexate; PBS; IP; rat; 2ML1; 7 days; Antibiotic; cancer; no stress (see p249).

P1707 Kimler,B.F., Martin,D.F., Evans,R.G., Morantz,R.A., Vats,T.S. Combination of radiation therapy and intercranial bleomycin in the 9L rat brain tumor model. Int.J.Radiat.Oncol.Biol.Phys. 1990; 18(--):1115-1121. >>> Bleomycin; CSF/CNS (intratumoral); cattle; rat; 2001; 2002; 7, 14 days; Antibiotic; controls received pumps with saline only; tissue perfusion (tumor); dose-response (graph, p. 1117); comparison of ip injections vs. mp.

P1211 Vanuytsel,L., Feng,Y., Landuyt,W., Begg,A., Van der Schueren,E. Effect of simultaneous administration of bleomycin on the acute skin reactions of mice after single and fractionated doses of radiation. Int.J.Radiat.Oncol.Biol.Phys. 1988; 14(--):103-108. >>> Bleomycin; Saline; SC; mice; 7 days; Antibiotic; Pump model not stated; concomitant radiation treatment; antibiotic.

R0077 Ray,N., Theeuwes,F. Implantable osmotically powered drug delivery systems. In 'Drug Delivery Systems: Fundamentals and Techniques,' P.Johnson and J.G.Lloyd-Jones (eds.), Ellis Horwood Ltd., Chichester, England and VCH Verlasgesellschaft mbH, Weinheim, Federal Republic of Germany 1987; (-Ch. 7-):120-138. >>> Antipyrine; bleomycin; dopamine HCl; melatonin; methotrexate, sodium; nicotine; prednisolone; radio-isotopes; valproic acid; 14C tracer; 3H tracer; IA; IP; SC; Mice, rabbit, rat; no duration posted; ALZA-authored; synoptic review of mp; post op. care (antibiotic); comparison of sc injections vs. mp infusion; pulsed delivery.

P1159 Harrison,J.H., Lazo,J.S. High dose continuous infusion of bleomycin in mice: a new model for drug-induced pulmonary fibrosis. J.Pharmacol.Exp.Ther. 1987; 243(-3-):1185-1194. >>> Bleomycin; Saline; SC; mice; 2001; 1 week; Antibiotic; controls received mp w/ vehicle; C57BL/6, BALB/C mice used; author states mp superior for these experiments; comparison of bolus inject. vs. sc inject. vs. mp infusion; antibiotic.

P1037 Wahlberg,P., Wennerberg,J., Alm,P., Biorklund,A., Trope,C. The effect of continuous bleomycin infusion on the growth and cell kinetics of heterotransplanted squamous cell carcinoma of the head and neck. Anticancer Res. 1987; 7(--):55-58. >>> Bleomycin; Saline; SC; mice; 7 days; Antibiotic; controls received mp with vehicle; half-life data; mice implanted with SCC tumor; cancer therapy; comparison of ip injections vs. mp infusion.

P0493 Osieka,R., Glatte,P., Schmidt,C.-G. Continuous infusion versus intermittent bolus injection of bleomycin in a human embryonal testicular cancer xenograft. Cancer Treat.Rep. 1984; 68(-5-):799-801. >>> Bleomycin; Saline; IP; mice; 2001; 1 week; Antibiotic; comparison of daily intermittent ip injec vs. ip mp infusion; dose-response data; cancer chemotherapy.

P0458 Osieka,V.R. Continuous infusion vs. bolus injection of bleomycin in a human testicular cancer xenograft system. Arzneimittelforschung (German, English summary) 1984; 34(-4-):460-464. >>> Bleomycin; Saline; IP; mice; 2001; 1 week; Antibiotic; cancer therapy; dose range of 10.5-42 mg/kg bleomycin; comparison of daily injec vs. mp infusion; full text is printed in German.

P0383 Kato,T., Mizutani,M., Ota,K. Effect of peplomycin by continuous infusion on Ehrlich carcinoma. Jpn.J.Cancer Chemother. 1983; 10(-3-):763-767. >>> Peplomycin; Bleomycin; IP; mice; 2001; 1 week; Antibiotic; comparison of daily and intermittent injec. vs. mp infusion; cancer chemotherapy.

P0075 Peng,Y.-M., Alberts,D.S., Chen,H.S., Mason,N., Moon,T.E. Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration. Br.J.Cancer 1980; 41(-4-):644-647. >>> Bleomycin; Saline; IP; mice; 6 days; Antibiotic; intermittent bolus injection ip vs. infusion; cancer.

P0017 Sikic,B.I., Collins,J.M., Mimnaugh,E.G., Gram,T.E. Improved therapeutic index of bleomycin when administered by continuous infusion in mice. Cancer Treat.Rep. 1978; 62(-12-):2011-2017. >>> Bleomycin; Saline; SC; Mice; 7,14 days; Comparison of bolus injections vs. SC minipump; study #1 infused for 7 days and study #2 infused for 14 days; cancer (lung carcinoma); peptides.

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4. Doxycycline

P8002 Tsai,C.H., Hong,J.H., Hsieh,K.F., Hsiao,H.W., Chuang,W.L., Lee,C.C., McBride,W.H., Chiang,C.S. Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer. Cancer Gene Therapy 2006; 13(-12-):1082-1092. >>> Doxycycline; PBS; SC; Mice; 2001; 7 days; Controls received mp w/ vehicle; cancer (prostate); animal info (C57BL/6J, 7-8 weeks old); paper states incorrect pump model.

P7937 Bartoli,M.A., Parodi,F.E., Chu,J., Pagano,M.B., Mao,D.L., Baxter,B.T., Buckley,C., Ennis,T.L., Thompson,R.W. Localized administration of doxycycline suppresses aortic dilatation in an experimental mouse model of abdominal aortic aneurysm. Annals of Vascular Surgery 2006; 20(-2-):228-236. >>> Doxycycline hydrochloride; Saline; SC; IP; aorta; Mice; 1002; 14 days; Controls received mp w/ vehicle; tissue perfusion (aorta); dose-response (table 1); comparison of oral vs. mp; half-life (p. 234), 26.5 hours; cardiovascular; animal info (C57BL/6J, male, 8-10 weeks old, 20-35 grams); catheter secured to a polyvinyl alcohol sponge positioned over the anterior surface of the aorta and secured to retroperitoneal tissues; (quote p. 233).

P7374 Mavragani,M., Brudvik,P., Selvig,K.A. Orthodontically induced root and alveolar bone resorption: inhibitory effect of systemic doxycycline administration in rats. European Journal of Orthodontics 2005; 27(-3-):215-225. >>> Doxycycline; SC; Rat; 2002; 7, 10, 14 days; Controls received no treatment; no stress (see pg. 217); enzyme inhibitor (collagenase); orthodontic appliance; agent also known as Doxylin; "The animals tolerated the appliance and the implanted mini-osmotic pump well. The incision wound from the implantation of the mini-osmotic pump was adequately healed by the day following surgery!" (p. 217).

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5. Gentamicin

P8198 Bakardjiev,A.I., Theriot,J.A., Portnoy,D.A. Listeria monocytogenes traffics from maternal organs to the placenta and back. PLoS Pathog 2006; 2(-6-):e66-. >>> Gentamicin sulfate; SC; Guinea-pig (pregnant); 2ML1; ; Functionality of mp verified by plasma levels taken; teratology; listeria.

P6918 Li,M., Ding,D.L., Zheng,X.Y., Salvi,R. Vestibular destruction by slow infusion of gentamicin into semicircular canals. Acta Oto-laryngologica 2004; 124(--):35-41. >>> Gentamicin; Hank's solution; Ear (semicircular canals); Chinchilla; 1007D; 7 days; Controls received mp w/ vehicle; Meniere's disease; microcatheter used; 27 gauge tubing used for cannulation; tissue perfusion (semicircular canals).

P6860 Drevets,D.A., Dillon,M.J., Schawang,J.S., van Rooijen,N., Ehrchen,J., Sunderkoetter,C., Leenen,P.J.M. The Ly-6Chigh monocyte subpopulation transports Listeria monocytogenes into the brain during systemic infection of mice. Journal of Immunology 2004; 172(-7-):4418-4424. >>> Gentamicin; PBS; Mice; 1-2 days.

P6392 Okuda,T., Sugahara,K., Shimogori,H., Yamashita,H. Inner ear changes with intracochlear gentamicin administration in guinea pigs. Laryngoscope 2004; 114(-4-):694-697. >>> Gentamicin; Saline; Ear (cochlea); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle; pumps replaced at day 7; pump contained saline only for the first seven days ; PE-10 used; tissue perfusion (cochlea).

P4880 Drevets,D., Jelinek,T.A., Freitag,N.E. Listeria Monocytogenes-infected phagocytes can initiate central nervous system infection in mice. Infection and Immunity 2001; March 2001(--):1344-1350. >>> Gentamicin sulfate; PBS; SC; mice; 1007D; 4-6 days; controls received no gentamicin treatment; dose response (graph p. 1346); immunology.

P4869 Wu,W.J., Sha,S.H., McLaren,J.D., Kawamoto,K., Raphael,Y., Schacht,J. Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hearing Research 2001; 158(--):165-178. >>> Kanamycin; Gentamicin; Saline; SC; rat; mice; 15 days; preliminary experiments on drug tolerance were carried out in mice using gentamicin; kanamycin infusion done in rats..

P4856 Hoffer,M.E., Allen,K., Kopke,R.D., Weisskopf,P., Gottshall,K., Wester,D. Transtympanic versus sustained-release administration of gentamicin: Kinetics, morphology, and function. Laryngoscope 2001; 111(--):1343-1357. >>> Gentamicin sulfate; Water, sterile; Ear; Chinchilla; 2001; 7 days; Dose-response (graph, table p. 1349); comparison of transtympanic injections vs. mp/; IntraEar catheter used; Meniere's Disease; Vertigo; tinnitus; tissue perfusion.

P5108 Allen,K.A, Hoffer,M.E, Wester,D.C. Inner ear localization of medicines delivered via the round window microcatheter. Proceedings of the 4th International Symposium on Meniere's Disease 1999; (--):613-617. >>> Gentamicin; Ear (round window membrane); chinchilla; 14 days; functionality of mp verified by perilymph gentamicin levels; IntraEAR catheter used; passive diffusion (microcatheter alone) vs. infusion via mp compared (p. 616); pump model not specified, but states pump duration was 7 days; "The catheter-pump system allows us to control the delivery of medicine to the inner ear." (p. 616); tissue perfusion (round window membrane).

P4125 Winkler,J., Power,A.E., Ramirez,G.A., Thal,L.J. Short-term and complete reversal of NGF effects in rats with lesions of the nucleus basalis magnocellularis. Brain Research 1998; 788(--):1-12. >>> Nerve growth factor; Cytochrome C; Gentamicin; CSF, artificial; Albumin, rat serum; CSF/CNS; rat; 2002; 7 weeks; long-term study, pumps replaced after 3.5 weeks; "the pumps were paraffin-coated in 13 mm of wax, resulting in a flow rate of 0.25 ul/h (p. 2); recomb. human NGF used; peptides.

P3604 Lorenzi,G., Gmunder,F.K., Cogoli,A. Cultivation of hamster kidney cells in a dynamic cell culture system in space (spacelab IML-1 mission). Microgravity Sci.Technol. 1993; VI/1(--):34-38. >>> NaHCO3; Glucose; HEPES; DMEM; Serum, fetal calf; Gentamicin; in vitro (cell culture); 2001; no duration posted; mp connected to cell culture chamber; "...the osmotic pump delivered sufficient fresh medium to support cell growth in the perfusion chambers." p. 37; spaceflight.

P1411 Houghton,D.C., English,J., Bennett,W.M. Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term 'subtherapeutic' gentamicin. J.Lab.Clin.Med. 1988; 112(--):694-703. >>> Gentamicin; Saline; IV (jugular); rat; 2ML4; 6 months and 1, 2, 3, 4, 8, 12, 16, 20, 24 weeks; dose-response; functionality of mp verified by serum concentration; long-term study; pump replaced every 28 days; toxicology/teratology.

P1382 Gmunder,F.K., Nordau,C.-G., Tschopp,A., Huber,B., Cogoli,A. Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space. J.Biotechnol. 1988; 7(--):217-228. >>> Culture media, DMEM; HEPES; Serum, fetal calf; Gentamicin; Glucose; in vitro (cell culture); 2001; 7 days; Mp connected to cell culture chamber; cytotoxicity described; spaceflight.

P0953 Hollenbach,S.J., DeGuzman,L.R., Bellamy,R.F. Early administration of methylprednisolone promotes survival in rats with intra-abdominal sepsis. Circ.Shock 1986; 20(-2-):161-168. >>> Clindamycin; Methylprednisolone; Gentamicin; Naloxone; Saline; SC; rat; 2001; 7 days; controls received mp w/saline; toxicology; multiple pumps per animal (3); comparison of bolus injections vs. mp infusion; antibiotic.

P0830 Tran Ba Huy,P., Bernard,P., Schacht,J. Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs. J.Clin.Invest. 1986; 77(--):1492-1500. >>> Gentamicin; Saline; IV (jugular); rat; 2001; 2ML1; 2, 10, 12, 14, and 24 days; comparison of single im injection vs. mp infusion; pump replaced every 6th day; mp connected to catheter in jugular vein; agent infused at 4 different doses; antibiotic.

P0331 Tran Ba Huy,P., Meulemans,A., Wassef,M., Manuel,C., Sterkers,O., Amiel,C. Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion. Antimicrob.Agents Chemother. 1983; 23(-2-):344-346. >>> Gentamicin; SC; rat; 2 days; Multiple pumps per animal (2); antibiotic.

P0147 Tran Ba Huy,P., Manuel,C., Meulemans,A., Sterkers,O., Amiel,C. Pharmacokinetics of gentamicin in perilymph and endolymph of the rat as determined by radioimmunoassay. J.Infect.Dis. 1981; 143(-3-):476-486. >>> Gentamicin; SC; rat; 6 days; Multiple pumps per animal (2); comparison of single im injection or iv pump vs. mp infusion; antibiotic.

P0032 Michelson,J.B., Nozik,R.A. Experimental endophthalmitis treated with an implantable osmotic minipump. Arch.Ophthalmol. 1979; 97(-7-):1345-1346. >>> Gentamicin sulfate; Eye (vitreous); rabbit; 4.5 days; mp model not stated; comparison of intravitreal injection vs. infusion; antibiotic; tissue perfusion.

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6. Mitomycin

P1993 Fu,K.K., Lam,K.N. Early and late effects of mitomycin C and continuous low-dose-rate irradiation on the mouse skin and soft tissues of the leg. Int.J.Radiat.Oncol.Biol.Phys. 1991; 21(--):1523-1528. >>> Mitomycin C; Saline; IP; mice; no duration posted; cancer.

P1874 Lu,X., Richardson,P.M. Inflammation near the nerve cell body enhances axonal regeneration. J.Neurosci. 1991; 11(-4-):972-978. >>> Mitomycin C; CSF/CNS (spinal cord, intrathecal); rat; no duration posted; no comment posted.

P1302 Kawano,S., Yano,S., Sakamoto,S., Ogata,J. Effect of continuous intravesical infusion of low-concentrated mitomycin-C on bladder carcinogenesis in rats treated with N-butyl-N-4-hydroxybutyl-nitrosamine. J.Urol. 1988; 139(--):1343-1346. >>> Mitomycin C; bladder; rat; 2ML2; 2 weeks; mp connected to catheter; dose-response (graph, text); comparison of twice weekly injections vs. mp infusion; functionality of mp verified by urine levels; cancer/immunology; tissue perfusion.

P0818 Murphy,W.M., Blatnik,A.F., Shelton,T.B., Soloway,M.S. Carcinogenesis in mammalian urothelium: changes induced by non-carcinogenic substances and chronic indwelling catheters. J.Urol. 1986; 135(-4-):840-844. >>> Mitomycin; Water; bladder; rat; 1 year and 3 weeks; pump replaced periodically; mp connected to bladder via catheter; tumors induced by infusion of water or agent; lesions reversible over time; long-term study; cancer; controls received surgery only; mps cultured upon removal; tissue perfusion.

P0422 Akaza,H., Murphy,W.M., Soloway,M.S. Bladder cancer induced by noncarcinogenic substances. J.Urol. 1984; 131(--):153-155. >>> Formalin, neutral buffered; Water; Cisplatin; Mitomycin C; Saline; Saline; bladder; rat; 2002; 1, 2, and 3 weeks; cancer; comparison of agents carcinogenic effects; empty mp used in one exp.; mp connected to catheter in bladder; confusion over length of pumping time-states 18-22 days for 14 day pump; tissue perfusion.

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7. Neomycin

P5489 Cuevas,P., Carceller,F., Diaz-Gonzalez,D., Cuevas,B., Fernandez,A., Garcia-Gomez,I., Dujovny,M. Inhibition of rat glioma growth by neomycin. Preliminary report. NEUROLOGICAL RESEARCH 2002; 24(-6-):522-524. >>> Neomycin; Kanamycin; Furosenide; PBS; ear (scala tympani); Guinea-pig; 2004; 26 days; Tissue perfusion (round window); functionality of mp verified by residual volume; diagram of pump and electrode assembly (p. 94); catheter patency assessed by passing fluid through the line at the end of the experiment; Neomycin infused in pilot study; Kanamycin and furosenide were co-infused in a second study.

P5009 Shinohara,T., Bredberg,G., Ulfendahl,M., Pyykko,I., Olivius,N.P, Kaksonen,R., Lindstrom,B., Altschuler,R., Miller,J.M. Neurotrophic factor intervention restores auditory function in deafened animals. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2002; 99(-3-):1657-1660. >>> Brain-derived neurotrophic factor; Ciliary neurotrophic factor; Neomycin;; Perilymph, artificial; Ear (scala tympani); guinea-pig; 2002; 26 days; controls received mp w/ vehicle; tissue perfusion (cochlea, scala tympani); pumps replaced at day 15; peptides; catheter filled with perilymph and 10% neomycin; pump filled with vehicle or neurotrophic factor solution; 48-hr infusion of neomycin to cause deafness followed by 12 or 26 day infusion of neurotrophic factor pump reservoir..

P4733 Conlon,B.J, Smith,D.W. Topical aminoglycoside ototoxicity: Attempting to protect the cochlea.. Acta Otolaryngol. 2000; 120(--):596-599. >>> Neomycin; lipoic acid, alpha; Saline; Ear (round window); Guinea-pig; 2ML4; 7 days; Controls received mp w/ vehicle; tissue perfusion (round window); no stress (see pg. 597); Neomycin antibiotic solution was 5%; micro polyurethane tubing used; the authors state that ALZET delivery system more closely approximates the clinical situation of repeated otic application, with minimal middle ear trauma..

P4101 Schindler,R.A., Gladstone,H.B., Scott,N., Hradek,G.T., Williams,H., Shah,S.B. Enhanced preservation of the auditory nerve following cochlear perfusion with nerve growth factor. Am.J.Otology 1995; 16(-3-):304-309. >>> Nerve growth factor; Neomycin; Saline; ear (cochlea); guinea-pig; 2 weeks; controls received mp w/vehicle; tissue perfusion (scala tympani); pulsed delivery; cannula/catheter filled with neomycin which was infused for the first 24 h; pump was filled with NGF; peptides.

P2567 Davies,E., Gladstone,H.B., Williams,H., Hradek,G., Shah,S.B., Schindler,R.A. A model for long-term intracochlear administration of pharmacologic agents. Am.J.Otology 1994; 15(-6-):757-761. >>> Neomycin; Horseradish peroxidase; Saline; ear (cochlea); guinea-pig; 2002; 2-14 days; no comment posted.

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8. Penicillin

P6354 Harrington,A.W., Leiner,B., Blechschmitt,C., Arevalo,J.C., Lee,R., Moerl,L., Meyer,M., Hempstead,B.L., Yoon,S.O., Giehl,K.M. Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2004; 101(-16-):6226-6230. >>> Antibody, anti-nerve growth factor, neutralizing mouse; serum; immunoglobulin-G; penicillin; streptomycin; PBS; CSF/CNS (cortex); Rat; 2001; 1 week; Controls received mp w/ vehicle.

P1263 Kimoto,M., Kindler,V., Higaki,M., Ody,C., Izui,S., Vassalli,P. Recombinant murine IL-3 fails to stimulate T or B lymphopoiesis in vivo, but enhances immune responses to T cell-dependent antigens. J.Immunol. 1988; 140(-6-):1889-1894. >>> Interleukin-3, recomb. mouse; Penicillin; Streptomycin; Glycerol; PBS; IP; SC; mice; 2001; 2002; 7 days, 2 weeks; controls received mp w/vehicle; 2002 mp infused IL-3 ip for 2 weeks, additional mps implanted sc; peptides; antibiotics; IL-3 infused simultaneously with penicillin and streptomycin.

P1074 Astry,C.L., Nelson,S., Karam,G.H., Summer,W.R. Interactions of clindamycin with antibacterial defenses of the lung. Am.Rev.Respir.Dis. 1987; 135(--):1015-1019. >>> Clindamycin HCl; Penicillin G; Sodium hydroxide; Water; SC; mice; 72 hours; Pump model not stated; controls received mp w/water; dose-response; mp primed overnight in PSB; 2 doses of agent infused; agent infused separately; antibiotic.

P0804 Kindler,V., Thorens,B., de Kossodo,S., Allet,B., Eliason,J.F., Thatcher,D., Farber,N., Vassalli,P. Stimulation of hematopoiesis in vivo by recombinant bacterial murine interleukin 3. Proc.Natl.Acad.Sci. 1986; 83(--):1001-1005. >>> Endotoxin, E. coli; Interleukin-3, recomb. mouse; Penicillin; Streptomycin; Glycerol; PBS; SC; mice; 3 and 7 days; infusion supplemented w/ip injections; interleukin activity in blood varible - aggregation in pump? (see p. 1004); mp infusion in normal and irradiated mice; half-life; peptides; antibiotic.

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9. Rapamycin

P7922 Segrelles,C., Moral,M., Lara,M.F., Ruiz,S., Santos,M., Leis,H., Garcia-Escudero,R., Martinez-Cruz,A.B., Martinez-Palacio,J., Hernandez,P., Ballestin,C., Paramio,J.M. Molecular determinants of Akt-induced keratinocyte transformation. ONCOGENE 2006; 25(-8-):1174-1185. >>> Rapamycin; PBS; BSA; SC; Mice (nude); 2002; 2 weeks; Cancer; animal info (nude, 5-6 weeks old, female).

P7354 Krahe,T.E., Medina,A.E., De Bittencourt-Navarrete,R.E., Colello,R.J., Ramoa,A.S. Protein synthesis-independent plasticity mediates rapid and precise recovery of deprived eye responses. Neuron 2005; 48(-2-):329-343. >>> Cycloheximide; rapamycin; tetrodotoxin; PBS; Ferret; 4 days; Controls received mp w/ vehicle; 0.25 ul model pump used.

P7287 Guba,M., Koehl,G.E., Neppl,E., Doenecke,A., Steinbauer,M., Schlitt,H.J., Jauch,K.W., Geissler,E.K. Dosing of rapamycin is critical to achieve an optimal antiangiogenic effect against cancer. TRANSPLANT INTERNATIONAL 2005; 18(-1-):89-94. >>> Rapamycin; DMSO; IP; Mice; 2002; 7-35 days; Controls received mp w/ vehicle; comparison of IP injections vs. mp; cancer (colon adenocarcinoma); "The most effective inhibition of tumor growth occurred in rapamycin-treated mice on the continuous pumping system.;" "Survival data also show the most positive effect with continuous drug delivery." P. 91.

P4566 Luo,H., Chen,H., Qi,S, Loh,D., Daloze,P., Veillette,A, Xu,D., Wu,J. De novo-developed T cells have compromised response to existing alloantigens: Using Ld-specific transgenic 2C T cells as tracers in a mouse heart transplantation model. The Journal of Immunology 1998; 161(--):73-82. >>> Rapamycin; IP; Mice; 14 days;; Immunology; heart transplantation.

P3996 Thompson,P., Xu,D., Brunette,I., Chen,H. Combined effect of rapamycin and cyclosporine in the prevention of rat corneal allograft rejection. Transplant.Proc. 1998; 30(--):1033-1035. >>> Rapamycin; Tween 80; IV (lumbar); rat; 2002; 14 days; transplantation; dose-response (p. 1034); immunology.

P3363 Tu,Y., Stepkowski,S.M., Chou,T.-C., Kahan,B.D. The synergistic effects of cyclosporine, sirolimus, and brequinar on heart allograft survival in mice. Transplantation 1995; 59(-2-):177-183. >>> Cyclosporin A; Rapamycin; Cremophor; Dimethylacetamide, N, N-; Tween 80; PEG 400; IV (jugular); mice; 1007D; 7, 14 days; pumps replaced after 7 days; immunology; CSA and rapamycin given singly and via same pump.

P2508 Ferraresso,M., Tian,L., Ghobrial,R., Stepkowski,R., Kahan,B.D. Rapamycin inhibits production of cytotoxic but not noncytotoxic antibodies and preferentially activates T helper 2 cells that mediate long-term survival of heart allografts in rats. J.Immunol. 1994; 153(--):3307-3318. >>> Rapamycin; Dimethylacetamide, N, N-; PEG 400; Tween 80; IV (lumbar); rat; 2002; 14 days; immunology; serum from rats treated with RAPA via minipumps used to inoculate secondary recipients.

P2048 Stepkowski,S.M., Tu,Y., Condon,T.P., Bennett,C.F. Blocking of heart allograft rejection by intercellular adhesion molecule-1 antisense oligonucleotides alone or in combination with other immunosuppressive modalities. J.Immunol. 1994; 153(--):5336-5346. >>> Oligodeoxynucleotide, phosphorothioate antisense; Cyclosporin A; Rapamycin; Oligodeoxynucleotide, scrambled; Cremophor; Tween 80; Dimethylacetamide, N, N-; PEG 400; IV (jugular); mice; 7,14 days; oligo of interest was IP-3082; controls received no treatment, unrelated oligo IP-1082, or scrambled oligo IP-4189; immunology; "...this study reports the first example of pharmacologic activity of an antisense PS-oligo by i.v. systemic administration in a model of a complex inflammatory process".

P3013 Di Joseph,J.F., Russo,R.J., Cochran,D.W. Osmotic pump delivery of rapamycin. Transplantation 1993; 55(-2-):450-452. >>> Rapamycin; Dimethylacetamide, N, N-; Tween 80; PEG 400; in vitro; 2002; 2 weeks; stability verified by in vitro testing and HPLC for 14 days; in vitro validation of functionality and rapamycin stability.

P2417 Roberge,F.G., Xu,D., Chan,C.-C., de Smet,M.D., Nussenblatt,R.B., Chen,H. Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction. Curr.Eye Res. 1993; 12(-2-):197-203. >>> Rapamycin; PEG 400; Tween 80; Dimethylacetamide, N, N-; IV (lumbar); rat; 2002; 14 days; immunology.

P2309 Hamashima,T., Yoshimura,N., Ohsaka,Y., Oka,T., Stepkowski,S.M., Kahan,B.D. In vivo use of rapamycin suppresses neither IL-2 production nor IL-2 receptor expression in rat transplant model. Transplant.Proc. 1993; 25(-1-):723-724. >>> Rapamycin; IV (lumbar); rat; 7 days; immunology.

P2289 Chen,H.J., Xu,D., Luo,H., Daloze,P.M. Reversal of ongoing heart, kidney, and pancreas allograft rejection and suppression of accelerated heart allograft rejection in the rat by rapamycin. Transplantation 1993; 56(-3-):661-666. >>> Rapamycin; DMA; PEG 400; Tween 80; IV (lumbar); Rat; 2002; 14 days; Immunology.

P2264 Ferraresso,M., Ghobrial,R., Stepkowski,S.M., Kahan,B.D. The mechanism of unresponsiveness to allografts induced by rapamycin and rapamycin/cyclosporine treatment in rats. Transplantation 1993; 55(-4-):888-894. >>> Cyclosporin; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween 80; IV (lumbar); rat; 2002; 14 days; immunology.

P2246 DiJoseph,J.F., Mihatsch,M.J., Sehgal,S.N. Influence of rat strain on rapamycin's kidney effects. Transplant.Proc. 1993; 25(-1-):714-715. >>> Cyclosporin A; Rapamycin; Cremophor; Dimethylacetamide; Ethanol; PEG 400; Tween; IV (jugular); rat; 2002; 2 weeks; controls received mp w/vehicle; functionality of mp verified by HPLC analysis; immunology.

P2245 Daloze,P.J., Chen,H., Luo,H., Xu,D., Shan,X., Wu,J. Rapamycin's long-term effects on humoral and cellular immune responses in the rat. Transplant.Proc. 1993; 25(-1-):721-722. >>> Rapamycin; PEG; IV (lumbar); rat; 28 days; controls received mp w/PEG; pumps replaced at day 14; immunology.

P2229 Chen,H., Wu,J., Xu,D., Luo,H., Daloze,P. Rapamycin reverses acute heart, kidney, and pancreas allograft rejection and prevents accelerated heart allograft rejection in the rat. Transplant.Proc. 1993; 25(-1-):719-720. >>> Rapamycin; Dimethylacetamide, N, N-; PEG 400; Tween; IV; rat; 2002; 14,28 days; controls received mp w/vehicle; immunology.

P2228 Chen,H., Wu,J., Luo,H., Daloze,P. Synergistic effect of rapamycin and cyclosporine in pancreaticoduodenal transplantation in the rat. Transplant.Proc. 1992; 24(-3-):892-893. >>> Rapamycin; IV (lumbar); rat; 14 days; immunology.

P2016 Stepkowski,S.M., Chen,H.F., Wang,M.E., Daloze,P., Kahan,B.D. Inhibition of host-versus-graft and graft-versus-host responses after small bowel transplantation in rats by rapamycin. Transplantation 1992; 53(-2-):258-264. >>> Cyclosporin; Rapamycin; Dimethylacetamide; PEG 400; Tween; IV (lumbar); rat; 2002; 14 days; tissue perfusion (allograft); immunology.

R0106 Chang J.Y., Sehgal,S.N., Bansbach,C.C. FK506 and rapamycin: novel pharmacological probes of the immune response. TIPS 1991; 12(--):218-223. >>> Rapamycin; rat; 14 days; immunology.

P3156 Chen,H.F., Wu,J.P., Luo,H.Y., Daloze,P.M. Reversal of ongoing rejection of allografts by rapamycin. Transplant.Proc. 1991; 23(-4-):2241-2242. >>> Rapamycin; Tween; Dimethylacetamide, N-N-; PEG 400; IV (lumbar); rat; 14 days; immunology.

P2015 Stepkowski,S.M., Chen,H., Daloze,P., Kahan,B.D. Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat. Transplantation 1991; 51(-1-):22-26. >>> Rapamycin; Dimethylacetamide; PEG 400; Tween 80; IA (innominate); IV (lumbar); rat; 2002; 14 days; tissue perfusion (allograft).

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10. Streptomycin

P7559 Chan,C.C.M., Khodarahmi,K., Liu,J., Sutherland,D., Oschipok,L.W., Steeves,J.D., Tetzlaff,W. Dose-dependent beneficial and detrimental effects of ROCK inhibitor Y27632 on axonal sprouting and functional recovery after rat spinal cord injury. Experimental Neurology 2005; 196(-2-):352-364. >>> Y27632; streptomycin; PBS, sterile; penicillin; CSF/CNS (intrathecal); Rat; 2002; 2 weeks; 2, 4 days; Controls received mp w/ vehicle; functionality of mp verified by ROCK inhibitory activity in CSF; dose-response (fig. 3); stability of Y27632 verified by ROCK inhibitory activity after 13 days in mp at 37 C; enzyme inhibitor (RHO Kinase); animal info (male, Sprague-Dawley); cervical 4/5 dorsal column transection; therapeutic treatment (SCI).

P5659 Horiike,O., Shimogori,H., Ikeda,T., Yamashita,H. Protective effect of edaravone against streptomycin-induced vestibulot oxicity in the guinea pig. European Journal of Pharmacology 2003; 464(-1-):75-78. >>> Streptomycin; Saline; Ear (cochlea); Guinea-pig; 2002; 24 hours; tissue perfusion (round window).

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11. Tetracycline

P2384 Freeman,K., Ludington Jr,J.R., Svec,T.A., Pinero,G.J., Hoover,J. Continuously infused calcium hydroxide: its influence on hard tissue repair. J.Endodontics 1994; 20(-6-):272-275. >>> Calcium hydroxide; Barium hydroxide; Tetracycline; Glycerol; bone (femur); rat; 4 weeks; no stress (see pg. 274); tissue perfusion; good methods.

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12. Tobramycin

P0820 Powell,S.H., Thompson,W.L., Luthe,M.A., Stern,R.C., Grossniklaus,D.A., Bloxham,D.D., Groden,D.L., Jacobs,M.R., DiScenna,A.O., Cash,H.A., Klinger,J.D. Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilimicin, and tobramycin. J.Infect.Dis. 1983; 147(-5-):918-932. >>> Tobramycin; IP; guinea-pig; rat; 2ML1; 7 days, 72 hours; comparison of single injection vs. mp infusion; mps primed in saline for 4 hours; studies also used dogs and humans; one study used rabbits w/ infusaid pumps; antibiotics.

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13. Tunicamycin

P4971 Orsini,G., Zalzal,Y., Nanci,A. Localized infusion of tunicamycin in rat hemimandibles: Alteration of the basal lamina associated with maturation stage ameloblasts. JOURNAL OF HISTOCHEMISTRY&CYTOCHEMISTRY 2001; 49(--):165-176. >>> Tunicamycin; Saline; bone (mandible); rat; 2001; ; controls received mp w/ vehicle; tissue perfusion (bony elevation over incisor);article incorrectly states use of 2001D pump, but states 7 day delivery period and pump; Tunicamycin is an antibiotic that interferes with N-glycosylation;.

P1695 Kubota,H., Asakura,M., Tsukamoto,T., Imafuku,J., Nishizaki,J., Sato,A., Nakanishi,J., Ogawa,Y., Hasegawa,K. Mechanisms of the B-adrenoceptor down-regulation by the treatment with antidepressants in the rat cerebral cortex: effects of continuous administration of antidepressants by an osmotic pump. Jpn.J.Psychiatry Neurol. 1990; 44(-1-):135-136. >>> Tunicamycin; Cycloheximide; Desipramine; Fluoxetine; Mianserin; Trazodone; CSF/CNS; SC; rat; 2001; 2ML1; 4-7 days; comparison of sc injections vs. mp; cyclo. and tunica. delivered icv for 5 days.

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References on the Administration of Antibiotics Using ALZET® Osmotic Pumps

1. Actinomycin D

2. Amikacin

3. Bleomycin

4. Doxycycline

5. Gentamicin

6. Mitomycin

7. Neomycin

8. Penicillin

9. Rapamycin

10. Streptomycin

11. Tetracycline

12. Tobramycin

13. Tunicamycin

Sterile Catheter Tubing for Infusion Studies

References on the Administration of Antibiotics Using
ALZET^® Osmotic Pumps