Lees P, Ayliffe T, Maitho T E, Taylor J B
Department of Physiology, Royal Veterinary College, North Mymms, Hatfield, Hertfordshire.
Res Vet Sci. 1988 Jan;44(1):57-67.
The absorption, metabolism and urinary excretion of phenylbutazone were investigated in six adult cattle in a cross-over study involving administration intravenously, intramuscularly and orally at a dose rate of 4.4 mg kg-1. Following intravenous injection plasma disposition was described by a three compartment open model with mean elimination half-life (t1/2 beta) and clearance (ClB) values of 35.9 hours and 2.77 ml kg-1 h-1, respectively. Somewhat longer t1/2 beta values were obtained after oral and intramuscular dosing and these may have resulted from sequestration within and slow absorption from the gastrointestinal tract and continual uptake from intramuscular sites following precipitation as a depot. Absorption was more complete after intramuscular than after oral dosing; area under curve values were almost twice as high for the intramuscular route. Double peaks in the plasma concentration time curves after oral dosing were recorded in some cows. These may have resulted from drug adsorption on to and subsequent desorption from hay or as a consequence of enterohepatic shunting. There was no evidence for opening of the oesophageal groove and direct passage of the drug into the abomasum. Two hydroxylated metabolites of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone were detected in trace amounts in plasma for 72 hours and in much higher concentrations in urine for 168 hours. Approximate urine:plasma (U/P) concentration ratios for the metabolites approached and occasionally exceeded the U/P ratio for endogenous creatinine, indicating poor reabsorption and, possibly, tubular secretion. Cumulative urinary excretion data indicated that the hydroxylated derivatives of phenylbutazone are probably formed more slowly in cattle than in horses.
在一项交叉研究中，以4.4 mg kg-1的剂量率对6头成年牛进行静脉注射、肌肉注射和口服给药，研究了保泰松的吸收、代谢和尿排泄情况。静脉注射后，血浆处置符合三室开放模型，平均消除半衰期（t1/2β）和清除率（ClB）分别为35.9小时和2.77 ml kg-1 h-1。口服和肌肉注射给药后获得的t1/2β值略长，这可能是由于药物在胃肠道内滞留、吸收缓慢以及沉淀为贮库后从肌肉部位持续摄取所致。肌肉注射后的吸收比口服给药更完全；肌肉注射途径的曲线下面积值几乎是口服途径的两倍。在一些奶牛口服给药后的血浆浓度-时间曲线上记录到双峰。这可能是由于药物吸附在干草上并随后解吸，或者是由于肝肠循环。没有证据表明食管沟开放以及药物直接进入皱胃。保泰松的两种羟基化代谢物，羟基保泰松和γ-羟基保泰松，在血浆中微量检测到72小时，在尿液中浓度更高，持续168小时。代谢物的尿：血浆（U/P）浓度比接近并偶尔超过内源性肌酐的U/P比，表明重吸收不良，可能还有肾小管分泌。累积尿排泄数据表明，保泰松的羟基化衍生物在牛体内的形成可能比在马体内更慢。
