Loft S, Poulsen H E, Sonne J, Døssing M
Department of Pharmacology, Gentofte Hospital, Copenhagen, Denmark.
Clin Pharmacol Ther. 1988 Apr;43(4):420-8. doi: 10.1038/clpt.1988.53.
After 96 administrations of metronidazole to 36 subjects, it was found that the clearance could be determined from one plasma sample, the dose, and a volume of distribution estimated from sex, age, body weight, and height, without loss of precision and accuracy compared with conventional clearance determinations (r greater than 0.97). In 230 sample pairs the plasma and saliva concentrations of metronidazole were identical (r = 0.99). In 119 subjects the one-sample clearance of metronidazole was unimodally distributed. Body weight (r = 0.28) and the alcohol consumption (r = 0.23) correlated with the metronidazole clearance. In the same subjects the consumption of tobacco (r = 0.28), alcohol (r = -0.19), coffee/tea (r = 0.27), age (r = -0.24), and sex (r = 0.28) correlated with the antipyrine clearance. The clearances of metronidazole and antipyrine were correlated (r = 0.34). The differential influence of the environmental factors on the elimination rates supports differential metabolism of metronidazole and antipyrine.
在对36名受试者进行96次甲硝唑给药后发现,可从一份血浆样本、给药剂量以及根据性别、年龄、体重和身高估算的分布容积来确定清除率,与传统的清除率测定方法相比,精度和准确性并无损失(相关系数r大于0.97)。在230对样本中,甲硝唑的血浆浓度和唾液浓度相同(r = 0.99)。在119名受试者中,甲硝唑的单样本清除率呈单峰分布。体重(r = 0.28)和酒精摄入量(r = 0.23)与甲硝唑清除率相关。在相同受试者中,烟草消耗量(r = 0.28)、酒精(r = -0.19)、咖啡/茶(r = 0.27)、年龄(r = -0.24)和性别(r = 0.28)与安替比林清除率相关。甲硝唑和安替比林的清除率相关(r = 0.34)。环境因素对消除率的不同影响支持了甲硝唑和安替比林的代谢差异。