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In vivo PK / Pharmacokinetic studies

Pharmacokinetics describes the relationship between drug concentration and time in an organism following administration.

Explicitly, pharmacokinetics is the study of drug absorption, distribution, metabolism and elimination (ADME). Typically, the first in vivo experiment during an oral drug discovery project would be a single IV bolus dose in a pre-clinical species. This would already allow the determination of key PK parameters such as AUC, Cmax, t½, Vss and clearance. After a test compound has successfully passed this first PK hurdle, further PK studies are used to build a more detailed picture of all aspects of ADME. Oral PK, in combination with the above IV data allows the determination of oral bioavailability (F). Low oral F can be caused by poor absorption and/or high first-pass hepatic elimination. Collection of urine or bile allows calculation of renal and biliary clearance and identification of metabolites.

The following example shows typical IV and PO pharmacokinetic profiles.

Figure 1 – Cytotoxicity is indicated by decreased reduction of Resazurin to its measurable, fluorescent product Resorufin

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