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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Human pharmacokinetics and antimicrobial activities of the temocillin epimers.

The pharmacokinetics of the epimers of temocillin were investigated in 4 healthy male subjects following intravenous administration of 1g of temocillin disodium (free acid) which contains a R : S epimer ratio of approximately 65 : 35. The R epimer had a 2-fold greater total plasma clearance, a 23% larger volume of distribution and a shorter beta half-life than the S epimer. Intermediate values were obtained for total temocillin (R + S) from high pressure liquid chromatography (HPLC) data. In each plasma sample, the unbound fraction of the R epimer was generally 2-fold higher than that of the S epimer, which is suggested as the reason for the differences in the pharmacokinetic properties of the epimers. The temocillin pharmacokinetic parameters obtained from the microbiological assay data reflect most closely those for the R epimer derived from HPLC data. The resolved R epimer exhibited twice the potency of the S epimer against the microbiological assay organism Pseudomonas aeruginosa NCTC 10701. However, in tests for antibacterial susceptibility, for instance minimum inhibitory concentration (MIC) determinations involving prolonged incubation, there was little difference in the inhibitory activities of the resolved R and S epimers compared with temocillin (R + S), presumably as a consequence of the epimerization of the individual epimers. In contrast, in rapid tests for bactericidal activity, which minimise the effect of epimerization, the R epimer exhibited greater bactericidal activity than the S epimer.[1]


  1. Human pharmacokinetics and antimicrobial activities of the temocillin epimers. Guest, E.A., Horton, R., Mellows, G., Slocombe, B., Swaisland, A.J., Tasker, T.C., White, A.R. Drugs (1985) [Pubmed]
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