Drug Pharmacokinetic Comparison between Humans and Monkeys

Posted by cdavenport on Thursday Jan 21, 2010 Under ADME, Drug Safety

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.  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.  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.  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

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3 Responses to “Drug Pharmacokinetic Comparison between Humans and Monkeys”

  1. Deven Says:

    Thank you for posting this artilce.

  2. Greg Russell-Jones Says:

    Can you list the 8 that were greater? It is a case of different intestinal pH? Were the ones that were more bioavailable also acid/base titratable?

  3. cdavenport Says:

    Greg,

    Thanks for your excellent questions! I only have access to the same information that you do in the citation given. Your questions are among a list of pertinent questions that we should all be asking prior to selection of the appropriate toxicology species.

    Thanks for joining the discussion!

    Cynthia

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