Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers

被引:54
作者
Lotsch, J [1 ]
Stockmann, A [1 ]
Kobal, G [1 ]
Brune, K [1 ]
Waibel, R [1 ]
Schmidt, N [1 ]
Geisslinger, G [1 ]
机构
[1] UNIV ERLANGEN NURNBERG,DEPT PHARMACEUT CHEM,D-8520 ERLANGEN,GERMANY
关键词
D O I
10.1016/S0009-9236(96)90058-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Steady-state pharmacokinetics of morphine and morphine-6-glucuronide (M-6-G) after intravenous administration of either morphine or M-6-G were determined in healthy volunteers, With a dosing regimen calculated on the basis of data obtained in a first series of experiments in four subjects (morphine: intravenous loading dose of 0.24 mg/kg for 5 minutes and an intravenous infusion of 0.069 mg . kg(-1) . hr(-1) for 4 hours; M-6-G: loading dose of 0.011 mg/kg for 5 minutes and an infusion of 0.006 mg . kg(-1) . hr(-1) for 4 hours), it was possible to yield plasma concentrations of morphine and M-6-G in another four subjects close to predefined targeted levels (35 and 45.5 ng/ml morphine and M-6-G, respectively). This dosing regimen may be used in further pharmacodynamic studies to compare the analgesic effects of morphine and M-6-G, In addition, metabolite kinetics of M-S-G were calculated as a function of time with use of a linear systems approach to the estimation of rate and fraction of morphine glucuronidation to M-6-G.
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收藏
页码:316 / 325
页数:10
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