Studies Including Information on the Stability of Agents in ALZET® Osmotic Pumps

16304 Bazargan, M., Foster, D. J., Muhlhausler, B. S., Morrison, J. L., McMillen, I., Davey, A. K. Limited fetal metabolism of rosiglitazone: Elimination via the maternal compartment in the pregnant ewe. Reprod Toxicol 2016; 61(--):162-8. >>> Rosiglitazone Maleate; Water, Ethanol; SC; Sheep (pregnant); 2ML1; animal info (Singleton pregnant sheep); functionality of mp verified by plasma level, amniotix fluid samples; 15% ethanol used; Multiple pumps per animal (4); stability verified by regular plasma level measurements (reached after day 5, tested through day 16; half life of 24-48 hours in sheep); Catheters flushed with heparinized saline; Dose (2.7 mg/fetus/d);.

16291 Clermont, A., Murugesan, N., Zhou, Q., Kita, T., Robson, P. A., Rushbrooke, L. J., Evans, D. M., Aiello, L. P., Feener, E. P. Plasma Kallikrein Mediates Vascular Endothelial Growth Factor-Induced Retinal Dysfunction and Thickening. Invest Ophthalmol Vis Sci 2016; 57(-6-):2390-9. >>> Fluoroacetate, Propionamide ditri-; PEG 400, PBS; SC; Rat, mice; 1003D, 1007D; Controls received mp w/ vehicle; animal info (Male Sprague-Dawley (SD) rats 10 wks, plasma prekallikrein gene-deficient mice (KLKB1-/-)); functionality of mp verified by enzyme activity assays; 10% PEG 400 used; dose-response (pg 2394, 2398); stability verified by (single bolus subcutaneous injection); Fluoroacetate, Propionamide ditri- aka VA999272; enzyme inhibitor (PKal inhibitor); enzyme inhibitor (PKal inhibitor); Resultant plasma level (pg 2394);.

16149 Pan, Y., Daito, T., Sasaki, Y., Chung, Y. H., Xing, X., Pondugula, S., Swamidass, S. J., Wang, T., Kim, A. H., Yano, H. Inhibition of DNA Methyltransferases Blocks Mutant Huntingtin-Induced Neurotoxicity. Sci Rep 2016; 6(--):31022. >>> Cytidine, fluorodeoxy-; Saline; CSF/CNS; Mice; 2001; ALZET brain infusion kit 3 used; neurodegenerative (Huntington’s disease); stability verified by (“…FdCYd fully maintained its neuroprotective activity after 45 days of pre-incubation” see supplement 2); “…decitabine and FdCyd, are known to be degraded rapidly by cytidine deaminase in the liver (in vivo half life of decitabine<20 min)62, indicating that systemic administration may not be an effective strategy for drug delivery to the brain. We therefore chose intracerebroventricular (icv) administration using an Alzet osmotic pump, which provides continuous infusion of drug at a consistent rate from a subcutaneous pump” pg 8; FdCyd aka Cytidine, fluorodeoxy-; decitabine and FdCyd are similar in structure.

16076 Zadina, J. E., Nilges, M. R., Morgenweck, J., Zhang, X., Hackler, L., Fasold, M. B. Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine. Neuropharmacology 2016; 105(--):215-27. >>> Morphine; endomorphine analog; Saline; CSF/CNS (intrathecal); rat; 2001; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-400g); half-life (p. 219); behavioral testing (tail flick test; rotarod testing); stability verified by (internal testing; stability>1 year at 37C); pumps primed in 37C saline for 16 hours; used PE-8 IT catheter; Dose (2 ug/hr morphine; 0.056-0.075 ug/hr analog);.

15972 Lahmann, C., Kramer, H. B., Ashcroft, F. M. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents. PLoS One 2015; 10(-7-):e0134476. >>> Glibenclamide; CSF, artifical; DMSO; BSA; CSF/CNS; Rat; Mice; 2ML4; 2004; Controls received mp w/ vehicle; animal info (mice nV57M, 11-14 weeks old, 25-30g; rats male Lister-hooded, young adults, 200-300g); functionality of mp verified by plasma levels; rats ALZET brain infusion kit 2 used; mice ALZET brain infusion kit 3 used; 0.1% DMSO used; stability verified by (in vitro experimentation see pg 9); Cannula placement verified via histological analysis;.

15839 Christine Weber, Stephanie B. Telerman, Andreas S. Reimer, Ines Sequeira, Kifayathullah Liakath-Ali, Esther N. Arwert, Fiona M.Watt  Cancer Res 2016; 76(-4-):805-817. >>> arginine, N(omega)-hydroxy-nor-l; SC; Mice; 1004; animal info (InvEE); functionality of mp verified by plasma levels; stress/adverse reaction: (see pg. 811); stability verified by (10 days see pg 811); immunology;“Continuous dosing at a rate of 0.25 mL per hour ensured constant compound levels. Successful ARG1 inhibition was confirmed in blood plasma and wounded skin samples taken 5 days after implantation” pg 811; nor-NOHA aka N(omega)-hydroxy-nor-l-arginine;.

15831 John P. Valenta and Rueben A. Gonzales  ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 2016; 40(-1-):. >>> Monocyte chemoattractant protein-1, recombinant rat; CSF, artificial; water, distilled; albumin, rat serum; CSF/CNS; Rat; 1004; Controls received mp w/ vehicle; animal info (male, Long Evans, 350g); functionality of mp verified by ELISA and manufacturers instructions see pg189; ALZET brain infusion kit 2 used; dose-response (pg.190); post op. care (bupivicane intradermally; bupivacaine and gentamicin dripped into wound); behavioral testing (alcohol self administration); stability verified by (ELISA pg 192); cyanoacrylate adhesive;“We chose the ICV method to simulate the presence of brain-induced MCP-1 and the method’s ability to target the whole brain with molecules that do not readily cross the BBB” pg 188-189; pumps primed at 37C sterile saline; Dose (0.2, 20, 2000 ng/day);.

15775 H. JIA,, F. FRANCOIS,, J. BOURIEN,, M. EYBALIN,, R. V. LLOYD, T. R. VAN DE WATER,, J.-L. PUEL, F. VENAIL  neuroscience 2016; 316(--):261-278. >>> Dexamethasone; Ara-C; Perilymph, artificial; Ear (cochlea); Rat; 2001; Controls received mp w/ vehicle; animal info (Wistar, adult); animal info (Wistar, adult); stability verified by (incubation in 37C saline for 7 days see pg 268); one cochlea received vehicle only, while other recieved drug;.

15142 Williams, B.A., Butt, M.T., Zeller, J.R., Coffee, S., Pippi, M.A., Williams, B.A. Multimodal Perineural Analgesia with Combined Bupivacaine-Clonidine-Buprenorphine-Dexamethasone: Safe In Vivo and Chemically Compatible in Solution. PAIN MEDICINE 2015; 16(--):186-198. >>> Bupivacaine; clonidine; dexamethasone; Saline; CSF/CNS (sciatic nerve); Rat; 2ML1; Controls received mp w/ vehicle; animal info (male, albino, CD[SD]); no stress (see pg. 192); post op. care (IM butorphanol tartrate 0.05 mg/kg, ceftiofur sodium 5 mg/kg); stability verified by (pg. 195); used polyurethane catheter 0.5mm ID 0.9 mmOD; pumps removed after 1 week; dose (66.6 ug/mL).

15115 Tognini, P., Napoli, D., Tola, J., Silingardi, D., la Ragione, F., D'Esposito, M., Pizzorusso, T., Pizzorusso, T. Experience-dependent DNA methylation regulates plasticity in the developing visual cortex. NATURE NEUROSCIENCE 2015; 18(--):956-+. >>> RG108; Cyclodextrin, 2-hydroxypropyl-b-; CSF/CNS; Mice; 1007D; Controls received mp w/ vehicle; animal info (C57BL6J, P25); 5% cyclodextrin used; stability verified by (37C t1/2 of 20 days); enzyme inhibitor;.

14715 Dugan, L.L., Tian, L.L., Quick, K.L., Hardt, J.I., Karimi, M., Brown, C., Loftin, S., Flores, H., Moerlein, S.M., Polich, J., Tabbal, S.D., Mink, J.W., Perlmutter, J.S., Perlmutter, J.S. Carboxyfullerene Neuroprotection Postinjury in Parkinsonian Nonhuman Primates. Annals of Neurology 2014; 76(--):393-402. >>> C3; SC; IP; Monkey (macaque); 2ML4; Controls received mp w/ placebo; animal info (Macaca facicularis); Multiple pumps per animal (2); neurodegenerative (Parkinson's disease); behavioral testing (locomotor activity); stability verified by (testing at 37C, C3 is stable for>40 days); Carboxyfullerine aka C3;.

13963 Takeda, T., Fujii, M., Hattori, Y., Yamamoto, M., Shimazoe, T., Ishii, Y., Himeno, M., Yamada, H. Maternal Exposure to Dioxin Imprints Sexual Immaturity of the Pups through Fixing the Status of the Reduced Expression of Hypothalamic Gonadotropin-Releasing Hormone. MOLECULAR PHARMACOLOGY 2014; 85(-1-):74-82. >>> Gonadotropin-releasing hormone; Saline; HCl; CSF/CNS; Rat; 2002; Controls received mp w/ vehicle; animal info (male, Wistar, PND63); ALZET brain infusion kit 2 used; behavioral testing (sexual behavior); stability verified by (incubation of GnRH at 37C for 2 weeks - half of GnRH remains in unchanged form pg.78); teratology; Cannula placement verified via 0.1% infusion of bromophenol blue; 0.1 M HCl.

13922 Savolainen, M.H., Richie, C.T., Harvey, B.K., Maennistoe, P.T., Maguire-Zeiss, K.A., Myoehaenen, T.T., Myoehaenen, T.T. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. NEUROBIOLOGY OF DISEASE 2014; 68(--):1-15. >>> KYP-2047; DMSO; saline; IP; Mice (transgenic); Controls received mp w/ vehicle; animal info (Snca tm(A30P) or WT, 12-13 months old); functionality of mp verified by decrease in PREP activity; 50% DMSO used; neurodegenerative (Parkinson's disease; Lewy body dementia); post op. care (buprenorphine); stability verified by (stability experiment one month); pumps primed overnight in 37C saline; KYP-2047 is a enzyme inhibitor (PREP);.

13916 Roman, C.W., Lezak, K.R., Hartsock, M.J., Falls, W.A., Braas, K.M., Howard, A.B., Hammack, S.E., May, V., May, V. PAC1 receptor antagonism in the bed nucleus of the stria terminalis (BNST) attenuates the endocrine and behavioral consequences of chronic stress. Psychoneuroendocrinology 2014; 47(--):151-165. >>> Pituitary adenylate cyclase activating polypeptide; Saline; BSA; CSF/CNS; Rat; 2002; Animal info (male, adult); behavioral testing (novel object recognition, open field, elevated plus maze); stability verified by (radioimmunoassays; 4% loss per day); cardiovascular; Cannula placement verified via crestyl violet staining and visual inspection; pituitary adenylate cyclase activating polypeptide aka PACP (6-38); delayed delivery; catheters filled with vehicle; pumps primed; PACAP (6-38) is a PAC1 receptor antagonist; stress; y-connector; PACAP (6-38)75uM;.

13726 Calcagnoli, F., Meyer, N., de Boer, S.F., Althaus, M., Koolhaas, J.M., Calcagnoli, F. Chronic enhancement of brain oxytocin levels causes enduring anti-aggressive and pro-social explorative behavioral effects in male rats. Hormones and Behavior 2014; 65(--):427-433. >>> Oxytocin, synthetic; antagonist, peptidergic oxytocin; Saline, sterile, pyrogen-free; CSF/CNS; Rat; 1007D; Controls received mp w/ vehicle; animal info (male, Groningen, adult); ALZET brain infusion kit 2 used; behavioral testing (resident intruder test); stability verified by (pilot study; 44% destruction of OVT over 10 day period in vivo); peptides; Cannula placement verified via dye injection after sacrifice; Plastics One guide cannula; dental acrylic cement and two stainless steel screws; pumps and catheters incubated in room temperature saline overnight;.

13717 Ben Menachem-Zidon, O., Ben Menahem, Y., Ben Hur, T., Yirmiya, R. Intra-Hippocampal Transplantation of Neural Precursor Cells with Transgenic Over-Expression of IL-1 Receptor Antagonist Rescues Memory and Neurogenesis Impairments in an Alzheimer's Disease Model. Neuropsychopharmacology 2014; 39(-2-):401-414. >>> Interleukin-1, receptor antagonist; CSF/CNS; Mice (transgenic); Controls received mp w/ vehicle; animal info (WT and Tg2576, 11 months old); pumps replaced every 2 weeks; ALZET brain infusion kit 3 used; neurodegenerative (Alzheimer's disease); behavioral testing (fear conditioning; morris water maze); stability verified by (IL-1-ra remains effective for 2 weeks in pumps); Used three anchoring screws;.

13665 Walters, M.J., Ebsworth, K., Berahovich, R.D., Penfold, M.E.T., Liu, S.C., Al Omran, R., Kioi, M., Chernikova, S.B., Tseng, D., Mulkearns-Hubert, E.E., Sinyuk, M., Ransohoff, R.M., Lathia, J.D., Karamchandani, J., Kohrt, H.E.K., Zhang, P., Powers, J.P., Jaen, J.C., Schall, T.J., Merchant, M., Recht, L., Brown, J.M. Inhibition of CXCR7 extends survival following irradiation of brain tumours in mice and rats. British Journal of Cancer 2014; 110(-5-):1179-1188. >>> CCX662; SC; Rat (pregnant); 2004; Controls received mp w/ vehicle; animal info (Sprague Dawley, 115 days old); functionality of mp verified by plasma levels sampled at 9 and 16 days post implantation; pumps replaced every 7 days; cancer (glioblastoma); stability verified by (IC90 value after 16 days); CCX662 is a CXCR7 inhibitor.

13640 Grommes, C., Karlo, J.C., Caprariello, A., Blankenship, D., DeChant, A., Landreth, G.E. The PPARgamma agonist pioglitazone crosses the blood-brain barrier and reduces tumor growth in a human xenograft model. Cancer Chemotherapy and Pharmacology 2013; 71(-4-):929-936. >>> Pioglitazone; Dulbecco's modified eagle medium; CSF/CNS; Mice (SCID); 2004; Controls received mp w/ vehicle; animal info (Balb/CJHanHsd-Prkdc-SCID, 6 weeks old); ALZET brain infusion kit used; comparison of oral dosing vs mp; cancer (tumors); dose-response (CNS); stability verified by (p.934 - incubation at 37C for 21 days);"Intracerebral treatment with 1 lM pio prolonged survival significantly from 49 to 68 days... This defines the minimal effective dose for oral pio treatment at 240 PPM (20.2 mg/kg) and for intracerebral pio treatment at 1 lM (0.11 ug/kg)."pg 932;.

13532 Ke, J.T., Li, M., Xu, S.Q., Zhang, W.J., Jiang, Y.W., Cheng, L.Y., Chen, L., Lou, J.N., Wu, W. Gliquidone decreases urinary protein by promoting tubular reabsorption in diabetic Goto-Kakizaki rats. Journal of Endocrinology 2014; 220(-2-):129-141. >>> Gliquidone; Dimethylformamide; IP; Rat; Animal info (male, SPF-grade, Goto-Kakizaki, 8 weeks old, 250-300g); functionality of mp verified by blood drug levels; 99.8% dimethylformamide used; comparison of intragastric administration vs mp (pg.133); stability verified by (plasma serum); diabetes;.

13488 Guo, X., Disatnik, M.H., Monbureau, M., Shamloo, M., Mochly-Rosen, D., Qi, X. Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration. Journal of Clinical Investigation 2013; 123(-12-):5371-5388. >>> P110-TAT; SC; Mice (transgenic); Controls received mp w/TAT control peptide; animal info (R6/2 HD model, 5 weeks old); functionality of mp verified by FITC positive signal in neurons pg 5379; pumps replaced every 28 days; neurodegenerative (Huntington's disease); no stress (see pg.5381, 5383); behavioral testing (motor function and behaviors); stability verified by (HPLC with UV detection for 28 days); long-term study; peptides; P110-TAT is a Drp1-selective peptide inhibitor.

12953 Geurts, L., Muccioli, G.G., Delzenne, N.M., Cani, P.D. Chronic Endocannabinoid System Stimulation Induces Muscle Macrophage and Lipid Accumulation in Type 2 Diabetic Mice Independently of Metabolic Endotoxaemia. PLoS One 2013; 8(-2-):U622-U631. >>> HU210; Tween; saline; SC; Mice; 2006; Control animals received mp w/ vehicle; animal info (C57BL/6J, male, 9 wks old); HU210 is a potent agonist, a synthetic cannabinoid; functionality of mp verified via HPLC-HRMS in the brain tissue; stability verified (6 weeks, pg e55963); long-term study;.

12917 Morales-Medina, J.C., Dumont, Y., Bonaventure, P., Quirion, R. Chronic administration of the Y(2) receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat. Neuropeptides 2012; 46(-6-):329-334. >>> JNJ-31020028; DMSO; saline; CSF/CNS; Rat; 2002; Control animals received mp w/ saline; animal info (Sprague Dawley, male, 150-170 g, OBX); 1% DMSO used; stability verified (28 days) pg 330; JNJ-31020028 is a Y2 receptor antagonist.

12808 Yo, K., Yu, Y.M., Zhao, G.Z., Bonab, A.A., Aikawa, N., Tompkins, R.G., Fischman, A.J. Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2013; 304(-4-):E331-E341. >>> SS31; Saline; IV (jugular); Rat; Control animals received mp w/ vehicle; animal info (Sprague Dawley, male, 16-19 wks old, 400-500 g); peptides; stability verified via stable isotope dilution method ("more than 7 days").

12785 Zhu, X.X., Krasnow, S.M., Roth-Carter, Q.R., Levasseur, P.R., Braun, T.P., Grossberg, A.J., Marks, D.L. Hypothalamic signaling in anorexia induced by indispensable amino acid deficiency. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2012; 303(-12-):E1446-E1458. >>> SHU-9119; CSF/CNS; Rat; 2004; Control animals received mp w/ artificial CSF; animal info (Sprague Dawley, 7-8 wks old); ; brain infusion kit 2 used; stability verified (21 days, pg E1450).

12586 Kassel, K.M., Sullivan, B.P., Cui, W., Copple, B.L., Luyendyk, J.P. Therapeutic Administration of the Direct Thrombin Inhibitor Argatroban Reduces Hepatic Inflammation in Mice with Established Fatty Liver Disease. American Journal of Pathology 2012; 181(-4-):1287-1295. >>> Argatroban; Acetic acid, glacial; sodium acetate; PEG 400; SC; Mice; 2004; Control animals received mp w/ vehicle; animal info (LDLr -/-, male, 6 wks old); 20% PEG 400 used; stability verified (4 weeks); post op. care (buprenorphine HCl).

12460 Simard, J.M., Woo, S.K., Tsymbalyuk, N., Voloshyn, O., Yurovsky, V., Ivanova, S., Lee, R., Gerzanich, V. Glibenclamide-10-h Treatment Window in a Clinically Relevant Model of Stroke. TRANSLATIONAL STROKE RESEARCH 2012; 3(-2-):286-295. >>> Glibenclamide; DMSO; saline; NaOH; SC; Rat; 2001; Controls received mp w/ vehicle; animal info (Wistar, male, 250-275 g); 5.5 hour delayed delivery accomplished by connecting 5.5 ul volume PE60; functionality of mp verified by residual volume; 8% DMSO used; stability verified via spectrophotometry; ischemia (cerebral).

12350 Bas, E., Van de Water, T.R., Gupta, C., Dinh, J., Vu, L., Martinez-Soriano, F., Lainez, J.M., Marco, J. Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses. British Journal of Pharmacology 2012; 166(-6-):1888-1904. >>> Gentamicin; dexamethasone; melatonin; Ear (round window); Rat; 2001; Controls received mp w/ saline; animal info (Wistar, male, 220-250 g); stability verified after 7 days (data not shown).

12269 Yuan, Y., Kasar, S., Underbayev, C., Vollenweider, D., Salerno, E., Kotenko, S.V., Raveche, E. Role of microRNA-15a in autoantibody production in interferon-augmented murine model of lupus. MOLECULAR IMMUNOLOGY 2012; 52(-2-):61-70. >>> Interferon, alpha; interferon, gamma; PBS; BSA; SC; Mice; 2006; Animal info (13 wks old, female, B/W); pumps replaced after 8 weeks; long-term study; stability verified after 8 weeks;"residue IFNs from the pumps at the end of treatment were tested on IFN and IFN responsive cell lines and demonstrated that the in vivo conditions in the pump did not affect bioactivity of both IFNs (data not shown)"pg 63.

11847 Pedersen, S.L., Sasikumar, P.G., Chelur, S., Holst, B., Artmann, A., Jensen, K.J., Vrang, N. Peptide hormone isoforms: N-terminally branched PYY3-36 isoforms give improved lipid and fat-cell metabolism in diet-induced obese mice. JOURNAL OF PEPTIDE SCIENCE 2010; 16(-11-):664-673. >>> Peptide YY (3-36); peptide YY (3-36), isoform 2; peptide YY (3-36), isoform 3; Saline; SC; Mice; 1003D; 2002; Controls received mp w/ vehicle; animal info (male, DIO C57BL/6J, NMRI, 8-9 wks old); incorrectly listed Model 1003 pumps used; stability verified pg 667 (2, 7,. 14 days via HPLC); wound clips used.

11701 Liu, Y.L., Ford, H.E., Druce, M.R., Minnion, J.S., Field, B.C.T., Shillito, J.C., Baxter, J., Murphy, K.G., Ghatei, M.A., Bloom, S.R. Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents. International Journal of Obesity 2010; 34(-12-):1715-1725. >>> OXM6421; oxyntomodulin; Saline; SC; Rat; mice; 2001; Controls received mp w/ vehicle; animal info (Wistar, male, 250-300 g; DIO, male); peptides; stability verified by HPLC (7 days); OXM6421 is a long-acting oxyntomodulin (OXM) analogue; obesity.

 

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What researchers are saying...

“Mini-pumps were used to eliminate stress associated with multiple daily injections.” Akhter et al., Journal of Orthopaedic Research 2002;21:14-19.