STUDIES OF THE DIFFERENT METABOLIC PATHWAYS OF ANTIPYRINE IN MAN - ORAL VERSUS IV ADMINISTRATION AND THE INFLUENCE OF URINARY COLLECTION TIME
STUDIES OF THE DIFFERENT METABOLIC PATHWAYS OF ANTIPYRINE IN MAN - ORAL VERSUS IV ADMINISTRATION AND THE INFLUENCE OF URINARY COLLECTION TIME
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DOI：
10.1007/bf00542332
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发表时间：
1982-01-01
影响因子：
2.9
通讯作者：
BREIMER, DD
中科院分区：
文献类型：
--
作者：
DANHOF, M;VANZUILEN, A;BREIMER, DD
本文研究了6名健康志愿者静脉注射和口服安替比林500 mg后血浆、唾液和尿中主要代谢产物的药代动力学。来自血浆和唾液的数据表明，安替比林水溶液的口服生物利用度是完全的。从约3小时开始，唾液/血浆浓度比随时间变化保持恒定，口服后平均值为0.87，静脉给药后平均值为0.91。安替比林的药代动力学参数可以令人满意地建立唾液数据的基础上，虽然分布容积和清除率值略高。静脉内给药后，3.8 . ±. 48小时内，1.9%的剂量以原型安替比林形式经尿液排泄，24.9 ±。以4-羟基安替比林计6.3%，16.5 ±.去甲安替比林3.2%，13.0 ±。2.2%为3-羟甲基-安替比林，5.8 ±-。以3-羧基安替比林计为1.0%。口服给药后未观察到显着差异。根据代谢物尿排泄率曲线的线性部分计算的半衰期与经口和静脉给药的半衰期大致相同，并且与血浆和唾液中母体药物的消除半衰期具有相同的数量级。对于测定最终代谢物比率，采集至少36 h的尿液很重要，因为尿液中3-羟甲基-安替比林的排泄延迟。
The pharmacokinetics of antipyrine in plasma, saliva and urinary excretion of its major metabolites, were studied following i.v. and oral administration of antipyrine 500 mg to 6 healthy volunteers. Data from both plasma and saliva showed that the oral bioavailability of antipyrine given as an aqueous solution was complete. The saliva/plasma concentration ratio was constant with time from about 3 h onwards, with a mean value of 0.87 after oral and 0.91 after i.v. administration. The pharmacokinetic parameters of antipyrine can be satisfactorily established on the basis of salivary data, although the volume of distribution and clearance values were slightly too high. After i.v. administration, 3.8 .+-. 1.9% of the dose was excreted in urine as unchanged antipyrine in 48 h, 24.9 .+-. 6.3% as 4-hydroxyantipyrine, 16.5 .+-. 3.2% as norantipyrine, 13.0 .+-. 2.2% as 3-hydroxymethyl-antipyrine and 5.8 .+-. 1.0% as 3-carboxy-antipyrine. No significant differences were observed following oral administration. The half-lives calculated from the linear part of the urinary excretion rate curves of the metabolites were about the same for oral and i.v. administration and were of the same order of magnitude as the elimination half-life of parent drug in plasma and saliva. It is important for determination of the ultimate metabolite ratio that urine is collected for at least 36 h, because there is a delay in the excretion of 3-hydroxymethyl-antipyrine in urine.