Human pharmacokinetics of temocillin (BRL 17421) side chain epimers

The pharmacokinetics of the sidechain epimers of temocillin were investigated in four healthy male subjects following a single iv dose of temocillin disodium (1 g pure free acid) containing 64 2% R-epirner. Plasma and urinary concentrations of the epimers were determined by hplc methods. The R-epimer was twice as rapidly cleared, had a 23% larger volume of distribution and a 60% shorter β half-life than the S-epirner. Intermediate values were obtained for total temocillin (from hplc data). The differences in the pharmacokinetic properties of the epimers are most likely the result of different extents of plasma protein bindlng. In each plasma sample, the free fraction of the R-epimer was higher (up to two-fold) than that of the S-zpimer. In a companson of temocillin pharmacokmetic parameters derived from hplc and microbiological assay data, the values obtained from the latter analyses reflected most closely those for the R-epimer. Further indicahons that the Repimer is more microbiologically achve against Pseudomonas aeruginosa NMTC 10701 from other assessments of relative antibacterial activity are discussed