PHARMACOKINETICS OF THE ENANTIOMERS OF BUPIVACAINE FOLLOWING INTRAVENOUS ADMINISTRATION OF THE RACEMATE

被引:61
作者
BURM, AGL [1 ]
VANDERMEER, AD [1 ]
VANKLEEF, JW [1 ]
ZEIJLMANS, PWM [1 ]
GROEN, K [1 ]
机构
[1] NATL INST PUBL HLTH & ENVIRONM PROTECT,BIOTRANSFORMAT PHARMACO & TOXICOKINET UNIT,3720 BA BILTHOVEN,NETHERLANDS
关键词
BUPIVACAINE ENANTIOMERS; PHARMACOKINETICS; PROTEIN BINDING;
D O I
10.1111/j.1365-2125.1994.tb04335.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The pharmacokinetics of R(+)-bupivacaine and S(-)-bupivacaine were investigated following a 10 min intravenous infusion of the racemate (dose 30 mg) in 10 healthy males. 2 The fractions unbound of R(+)- and S(-)-bupivacaine in pre-dose plasma were determined for each subject after in vitro addition of rac-bupivacaine (concentration of each enantiomer: approximately 300 ng ml(-1)). 3 The total plasma clearance of R(+)-bupivacaine (mean +/- s.d.: 0.395 +/- 0.076 1 min(-1)) was greater (P < 0.0001) than that of S(-)-bupivacaine (0.317 +/- 0.067 1 min(-1)). The volumes of distribution of R(+)-bupivacaine at steady state (84 +/- 29 1) and during the terminal log-linear phase (117 +/- 47 1) were larger (P < 0.0002) than those of S(-)-bupivacaine (54 +/- 20 1 and 71 +/- 34 1, respectively). The terminal half-life (210 +/- 95 min) and mean residence time (215 +/- 74 min) of R(+)-bupivacaine were longer than those of S(-)-bupivacaine (157 +/- 77 min, P < 0.01, and 172 +/- 55 min, P < 0.02, respectively). 4 The free percentage of R(+)-bupivacaine (6.6 +/- 3.0 %) was greater (P < 0.0002) than that of S(-)-bupivacaine (4.5 +/- 2.1 %). 5 The plasma clearance of unbound R(+)-bupivacaine (7.26 +/- 3.60 1 min(-1)) was smaller (P < 0.01) than that of S(-)-bupivacaine (8.71 +/- 4.27 1 min(-1)). Volumes of distribution based on unbound R(+)-bupivacaine concentrations (Vu(ss): 1576 +/- 934 1; Vu: 2233 +/- 1442 1) did not differ from those of S(-)-bupivacaine (Vu(ss): 1498 +/- 892 1; Vu: 1978 +/- 1302 1). 6 The enantioselective systemic disposition of bupivacaine can to a large extent be attributed to differences in the degree of plasma binding of the enantiomers.
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收藏
页码:125 / 129
页数:5
相关论文
共 15 条
[11]   NON-COMPARTMENTAL DETERMINATION OF THE STEADY-STATE VOLUME OF DISTRIBUTION FOR ANY MODE OF ADMINISTRATION [J].
PERRIER, D ;
MAYERSOHN, M .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1982, 71 (03) :372-373
[12]   THE APPLICATION OF STATISTICAL MOMENT THEORY TO THE EVALUATION OF INVIVO DISSOLUTION TIME AND ABSORPTION TIME [J].
RIEGELMAN, S ;
COLLIER, P .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1980, 8 (05) :509-534
[13]   CARDIOVASCULAR EFFECTS AND REGIONAL CLEARANCES OF IV BUPIVACAINE IN SHEEP - ENANTIOMERIC ANALYSIS [J].
RUTTEN, AJ ;
MATHER, LE ;
MCLEAN, CF .
BRITISH JOURNAL OF ANAESTHESIA, 1991, 67 (03) :247-256
[14]   POSTOPERATIVE COURSE OF PLASMA-PROTEIN BINDING OF LIGNOCAINE, ROPIVACAINE AND BUPIVACAINE IN SHEEP [J].
RUTTEN, AJ ;
MATHER, LE ;
PLUMMER, JL ;
HENNING, EC .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1992, 44 (04) :355-358
[15]   STEREOSELECTIVE EFFECTS OF THE ENANTIOMERS OF BUPIVACAINE ON THE ELECTROPHYSIOLOGICAL PROPERTIES OF THE GUINEA-PIG PAPILLARY-MUSCLE [J].
VANHOUTTE, F ;
VEREECKE, J ;
VERBEKE, N ;
CARMELIET, E .
BRITISH JOURNAL OF PHARMACOLOGY, 1991, 103 (01) :1275-1281