in Vivo Pharmacology
“The majority of chemicals are eliminated considerably faster in small laboratory animals as compared with humans, and constant-rate infusion offers several advantages over conventional, bolus delivery regimens in compensating for this difference.” (Clarke D.O. Toxicology Methods 1993;3(4):223-25)
When testing a novel compound in vivo, rapid elimination can result in mistaken assessment of activity. Rats and mice generally eliminate test compounds more rapidly than humans. After a single injection, plasma concentration rises to a peak and then declines rapidly until the compound is eliminated from plasma and tissues. Often the duration of serum activity following a single injection is limited to several hours, hence biological effects either fail to develop or develop poorly.
- If no effect is observed following injection, it is difficult to determine whether the compound is inactive or if it simply was not present in adequate concentration and for a sufficient duration to elicit an effect.
- Depending on the rate of elimination and the frequency of dosing, injections can result in periods during which drug is absent from plasma and tissues. Such extreme variability in compound exposure over time can influence the expression of drug action.
Thus, the data from such experiments can be misleading as to the nature of compound effects and the dose required to elicit them. Additionally, repeated injections are stressful to the animal and difficult to maintain around the clock. ALZET pumps are drug discovery tools that offer researchers enhanced control over test compound levels in plasma and tissues. Through continuous infusion, these pumps maintain a well-defined, consistent pattern of drug exposure throughout the duration of the experiment. ALZET pumps ensure that test compounds are present in plasma and tissues for a sufficient duration to allow their biological effects to develop fully and reproducibly. The scientific literature contains many examples where ALZET pumps have facilitated full development of drug effects, including those of proteins, peptides, and other rapidly eliminated compounds.