FCE 22891作为口服前体药物给药后FCE 22101的药代动力学和代谢情况。

Pharmacokinetics and metabolism of FCE 22101 following its administration as the oral pro-drug FCE 22891.

作者信息

Lovering A M, MacGowan A P, Lewis D A, Reeves D S

机构信息

Department of Medical Microbiology, Southmead Hospital, Westbury on Trym, Bristol, UK.

出版信息

J Antimicrob Chemother. 1992 Feb;29(2):179-85. doi: 10.1093/jac/29.2.179.

DOI:10.1093/jac/29.2.179

PMID:1506334

Abstract

Ten healthy male volunteers who had previously received both intramuscular and intravenous doses of FCE 22101 received a single oral dose of FCE 22891, the acetoxymethyl ester and pro-drug of FCE 22101. After a lag time of 22 min, mean plasma levels of FCE 22101 rose with a T1/2 absorbance of 19 min to 2.5 mg/L at 30 min, 3.6 mg/L at 60 min and a Cmax of 4.6 mg/L at 80 min; levels then fell with a T1/2 beta of 29 min to be undetectable at 300 min. The mean area under the concentration-time curve (AUC) was 497 mg.min/L giving an absolute bioavailability for FCE 22101 of 32%. Neither FCE 22101 or its metabolites were present in any of the saliva samples collected at intervals up to 360 min after dosing. Mean urinary recoveries were FCE 22101 12% (+/- S.D. 4.6), P1 16% (+/- S.D. 9.1) and P2 3.3% (+/- S.D. 2.1). It was not possible to detect the pro-drug FCE 22891 in any of the blood or urine samples. Significant levels of the metabolite P1 were observed in blood with peak levels of 1.7 mg/L seen 130 min after dosing, 50 min later than the peak FCE 22101 levels, and giving a mean AUC of 297 mg.min/L.

摘要

十名此前已接受过肌肉注射和静脉注射FCE 22101的健康男性志愿者口服了一剂FCE 22891，它是FCE 22101的乙酰氧基甲酯和前体药物。经过22分钟的滞后时间后，FCE 22101的平均血浆水平开始上升，吸收半衰期为19分钟，30分钟时达到2.5毫克/升，60分钟时为3.6毫克/升，80分钟时Cmax为4.6毫克/升；随后水平下降，消除半衰期为29分钟，300分钟时无法检测到。浓度-时间曲线下的平均面积（AUC）为497毫克·分钟/升，FCE 22101的绝对生物利用度为32%。给药后长达360分钟内每隔一段时间采集的唾液样本中均未检测到FCE 22101或其代谢物。FCE 22101的平均尿回收率为12%（±标准差4.6），P1为16%（±标准差9.1），P2为3.3%（±标准差2.1）。在任何血液或尿液样本中均未检测到前体药物FCE 22891。在血液中观察到代谢物P1的显著水平，给药后130分钟时达到峰值水平1.7毫克/升，比FCE 22101的峰值水平晚50分钟，平均AUC为297毫克·分钟/升。