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Pharmacokinetics of thiopentone enantiomers following intravenous injection or prolonged infusion of rac‐thiopentone
Author(s) -
Cordato D. J.,
Gross A. S.,
Herkes G. K.,
Mather L. E.
Publication year - 1997
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 - 10.1046/j.1365-2125.1997.00567.x
Subject(s) - pharmacokinetics , enantiomer , volume of distribution , pharmacodynamics , anesthesia , pharmacology , chemistry , medicine , stereochemistry
Aims Thiopentone is administered as a racemate ( rac ‐thiopentone) for induction of anaesthesia as well as for neurological and neurosurgical emergencies. The pharmacokinetics and pharmacodynamics of rac ‐thiopentone have been extensively studied but the component R‐(+)‐ and S‐(−)‐ enantiomers, until very recently, have been largely ignored. Methods The present study analyses the pharmacokinetics of R‐(+)‐ and S‐(−)‐thiopentone in 12 patients given rac ‐thiopentone intravenously for induction of anaesthesia and five patients given a prolonged infusion of rac ‐thiopentone used for treatment of intracranial hypertension. Results The mean total body clearance (CL T ) and apparent volume of distribution at steady‐state ( V ss ) showed trends towards higher values for R‐(+)‐ than for S‐(−)‐thiopentone in both patient groups; CL T and V ss of unbound fractions of R‐(+)‐ and S‐(−)‐thiopentone, however, did not show these trends. The time courses of R‐(+)‐ and S‐(−)‐ thiopentone serum concentrations were so similar that EEG effect could not be attributed to one or other enantiomer. Serum protein binding for S‐(−)‐thiopentone was greater than for R‐(+)‐thiopentone ( P =0.02) and 24 h urinary excretion of R‐(+)‐thiopentone was greater than for S‐(−)thiopentone ( P =0.03). In one patient, concomitant measurement of CSF and serum thiopentone concentrations found that serum: CSF equilibration of unbound fractions of both enantiomers was essentially complete. Conclusions The study was unable to determine any pharmacokinetic difference of clinical significance between the R‐(+)‐ and S‐(−)‐thiopentone enantiomers and concludes that minor differences in CL T and V ss could be explained by enantioselective difference found in serum protein binding.