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Pharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate.
Author(s) -
Burm AG,
Meer AD,
Kleef JW,
Zeijlmans PW,
Groen K
Publication year - 1994
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1994.tb04335.x
Subject(s) - bupivacaine , pharmacokinetics , anesthesia , enantiomer , half life , local anesthetic , medicine , chemistry , pharmacology , stereochemistry
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 l min‐1) was greater (P < 0.0001) than that of S(‐)‐bupivacaine (0.317 +/‐ 0.067 l min‐1). The volumes of distribution of R(+)‐bupivacaine at steady state (84 +/‐ 29 l) and during the terminal log‐linear phase (117 +/‐ 47 l) were larger (P < 0.0002) than those of S(‐)‐bupivacaine (54 +/‐ 20 l and 71 +/‐ 34 l, 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 l min‐1). Volumes of distribution based on unbound R(+)‐bupivacaine concentrations (Vuss: 1576 +/‐ 934 l; Vu: 2233 +/‐ 1442 l) did not differ from those of S(‐)‐bupivacaine (Vuss: 1498 +/‐ 892 l; Vu: 1978 +/‐ 1302 l). 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.