ALZET pumps allow researchers to understand and optimize the key determinants of drug action, such as the level and duration of drug exposure, and the spatial drug distribution relative to the target tissue. By manipulating these variables, drug effects can be optimized early in preclinical development, allowing clinical studies to be conducted at lower cost and with better results.
A drug’s therapeutic index is a ratio reflecting the quotient of its therapeutic effects and adverse effects. Varying the schedule of administration can have a major influence on the therapeutic index of some drugs. Relative to bolus dosing, constant infusion can:
- Increase efficacy
- Reduce side effects
- Both increase efficacy and reduce side effects
All of these changes can increase a drug’s therapeutic index, improving its value as a pharmaceutical. One cannot assume, however, that infusion regimens are superior to injections for all drugs. The relationship between dose, regimen, and drug effect must be carefully explored for each drug. Dose-response testing, where the effects of one or more schedules of injections are compared with the effects of constant infusion, helps elucidate schedule-dependent drug effects. This type of testing has been termed the injection-infusion comparison (IIC) protocol. This protocol is an established method for optimizing the effectiveness of anticancer agents, and it is important in the preclinical testing of proteins, peptides, and other recombinant DNA products.
This graph simulates plasma levels of a compound administered by injection compared with infusion by ALZET pump. Injections often produces plasma levels that greatly exceed effective concentrations, which can result in toxicity and wasted compound. Likewise, the therapeutic effect vanishes between doses for compounds with short half-lives.
In Vivo Pharmacology
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.
If you require further information on these Osmotic Pumps, feel free to contact us at the following:
Telephone: 6273 7252
Email : firstname.lastname@example.org
Mobile: 9105 5786
Address: Blk 203A Henderson Road, Henderson Industrial Park, #02-03 S(159546)
To know how the Alzet Osmotic Pump works, Kindly watch the following Video: