In-vivo pharmacokinetic studies are done in rats, mice, rabbits and others like zebrafish systems. First Pass: Clinically, first-pass metabolism is important when the fraction of the dose administered escapes metabolism. The liver is usually assumed to be the major site of first-pass metabolism of a drug administered orally, but other potential sites are the gastrointestinal tract, blood, vascular endothelium, lungs, and the arm from which venous samples are taken.

The predictions of the models are similar when bioavailability is large but differ dramatically when bioavailability is small. Many clinically important drugs undergo considerable first-pass metabolism after an oral dose. One major therapeutic implication of extensive first-pass metabolism is that much larger oral doses than intravenous doses are required to achieve equivalent plasma concentrations.

Portal/Excretion: We use metabolic cages to collect urine and faeces which helps in understanding excretion profile of test compounds. Renal filtration accounts for most drug excretion. Drugs bound to plasma proteins remain in the circulation; only unbound drug is contained in the glomerular filtrate. Acidification of urine increases re-absorption and decreases excretion of weak acids, and, in contrast, decreases re-absorption of weak bases. Alkalinization of urine has the opposite effect. In some cases of overdose, these principles are used to enhance the excretion of weak bases or acids.