To verify the availability of pharmacokinetic parameters in cynomolgus monkeys, hepatic availability (Fh) and the fraction absorbed (Fa) multiplied by intestinal availability (Fg) were evaluated to determine their contributions to absolute bioavailability (F) after intravenous and oral administrations. These preclinical results were compared with those for humans using 13 commercial drugs for which human pharmacokinetic parameters have been reported. مواقع مراهنات كرة قدم  In addition, in vitro studies of these drugs, including membrane permeability, intrinsic clearance, and p-glycoprotein affinity, were performed to classify the drugs on the basis of their pharmacokinetic properties.

In the present preclinical study, monkeys had a markedly lower F than humans for 8 of 13 drugs. قواعد لعبة بوكر  Although there were no obvious differences in Fh between humans and monkeys, a remarkable species difference in FaFg was observed.  These results suggest that first-pass intestinal metabolism is greater in cynomolgus monkeys than in humans, and that bioavailability in cynomolgus monkeys after oral administration may be unsuitable for predicting pharmacokinetics in humans. الرهان على مباريات كرة القدم  A rough correlation was also observed between in vitro metabolic stability and Fg in humans.

Key: F (bioavailability), Fa (fraction absorbed), Fg (intestinal availability), Fh (hepatic availability).

Drugs examined: amitriptyline, dexamethasone, digoxin,  hydrochlorothiazide, ibuprofen,  lithium carbonate, midazolam, nifedipine,  propranolol, quinidine,  tacrolimus, timolol, and verapamil.

Source: Drug Metabolism and Disposition