Semrad S D, McClure J T, Sams R A, Kaminski L M
Department of Medical Sciences, University of Wisconsin, Madison 53706.
Am J Vet Res. 1993 Nov;54(11):1906-12.
Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after i.v administration of a single dose (5 mg/kg of body weight, i.v.). Elimination half-life was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 micrograms/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.
年龄、物种和疾病状态可能会显著改变药物的处置和清除。当在患病新生儿中使用治疗指数较低的药物时，这一点尤为重要。在静脉注射单剂量（5毫克/千克体重，静脉注射）后，测定了24至32小时龄健康和内毒素血症犊牛中保泰松的药代动力学变量。健康和内毒素血症犊牛的消除半衰期分别为207小时和168小时，清除率分别为0.708毫升/千克/小时和0.828毫升/千克/小时。以给定剂量（4小时内2微克/千克）静脉输注内毒素并未显著改变任何计算得出的药代动力学变量。在健康犊牛中，保泰松给药后血清血栓素B2浓度显著（P = 0.05）抑制3小时，在内毒素攻击的犊牛中抑制4小时。对健康和内毒素血症犊牛每日给予保泰松（10毫克/千克负荷剂量，然后9天内每天5毫克/千克）未能诱发任何与非甾体抗炎药中毒一致的病变。
