Pharmacokinetics of 3 formulations of meloxicam in cynomolgus macaques (Macaca fascicularis)

3种美洛昔康制剂在食蟹猴(Macaca fascicularis)体内的药代动力学

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作者:Cassondra Bauer, Patrice Frost, Stephen Kirschner

Abstract

Meloxicam is a commonly used COX2-preferential NSAID in both human and veterinary patients. Minimal information has been published regarding appropriate dosing in nonhuman primates. Here we investigated the pharmacokinetic parameters of 3 formulations of meloxicam in cynomolgus macaques. A single dose of meloxicam SR, an extended-release formulation purported to provide therapeutic levels for as long as 72 h, was compared with the intramuscular and oral formulations dosed for 3 consecutive days and as a single dose. The oral formulation, both over 3 d and as a single dose, yielded lower plasma levels and a shorter duration than did intramuscular and sustained-release subcutaneous formulations. The intramuscular formulation, both over 3 d and as a single dose, provided lower plasma levels and a shorter duration than did a sustained-release subcutaneous formulation. The sustained-release formulations generated the highest plasma concentrations for the longest periods of time. None of the formulations caused significant effects on kidney or liver function. Our results indicate that the sustained-release formulation of meloxicam can achieve an adequate steady-state plasma concentration for 2 to 3 d in nonhuman primates. The standard intramuscular formulation provides adequate plasma concentrations for 12 to 24 h, with waxing and waning levels associated with daily dosing. The oral formulation has limited utility in nonhuman primates because of low circulating levels of drug.

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