Agl. Burm et al., PHARMACOKINETICS OF THE ENANTIOMERS OF BUPIVACAINE FOLLOWING INTRAVENOUS ADMINISTRATION OF THE RACEMATE, British journal of clinical pharmacology, 38(2), 1994, pp. 125-129
1 The pharmacokinetics of R(+)-bupivacaine and S(-)-bupivacaine were i
nvestigated following a 10 min intravenous infusion of the racemate (d
ose 30 mg) in 10 healthy males. 2 The fractions unbound of R(+)- and S
(-)-bupivacaine in pre-dose plasma were determined for each subject af
ter in vitro addition of rac-bupivacaine (concentration of each enanti
omer: 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 7
1 +/- 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(+)-bupivac
aine (6.6 +/- 3.0 %) was greater (P < 0.0002) than that of S(-)-bupiva
caine (4.5 +/- 2.1 %). 5 The plasma clearance of unbound R(+)-bupivaca
ine (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(s
s): 1498 +/- 892 1; Vu: 1978 +/- 1302 1). 6 The enantioselective syste
mic disposition of bupivacaine can to a large extent be attributed to
differences in the degree of plasma binding of the enantiomers.