Bauer Cassondra, Frost Patrice, Kirschner Stephen
Texas Biomedical Research Institute, Southwest National Primate Research Center, San Antonio, Texas, USA.
J Am Assoc Lab Anim Sci. 2014 Sep;53(5):502-11.
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.
美洛昔康是一种在人类和兽医患者中常用的COX2选择性非甾体抗炎药。关于非人灵长类动物的适当剂量，已发表的信息极少。在此，我们研究了美洛昔康的3种制剂在食蟹猴中的药代动力学参数。将单剂量的美洛昔康缓释制剂（一种据称能提供长达72小时治疗水平的缓释制剂）与连续3天给药的肌肉注射和口服制剂以及单剂量给药进行比较。口服制剂无论是连续3天给药还是单剂量给药，其血浆水平均低于肌肉注射和缓释皮下制剂，且持续时间较短。肌肉注射制剂无论是连续3天给药还是单剂量给药，其血浆水平均低于缓释皮下制剂，且持续时间较短。缓释制剂在最长的时间段内产生最高的血浆浓度。所有制剂均未对肾功能或肝功能产生显著影响。我们的结果表明，美洛昔康的缓释制剂在非人灵长类动物中可在2至3天内达到足够的稳态血浆浓度。标准肌肉注射制剂可在12至24小时内提供足够的血浆浓度，且随着每日给药血浆水平会有波动。由于药物循环水平较低，口服制剂在非人灵长类动物中的效用有限。
