Guest E A, Horton R, Mellows G, Slocombe B, Swaisland A J, Tasker T C
J Antimicrob Chemother. 1985 Mar;15(3):327-36. doi: 10.1093/jac/15.3.327.
The pharmacokinetics of the side-chain 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-epimer. 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 beta half-life than the S-epimer. 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 binding. In each plasma sample, the free fraction of the R-epimer was higher (up to two-fold) than that of the S-epimer. In a comparison of temocillin pharmacokinetic parameters derived from hplc and microbiological assay data, the values obtained from the latter analyses reflected most closely those for the R-epimer. Further indications that the R-epimer is more microbiologically active against Pseudomonas aeruginosa NCTC 10701 from other assessments of relative antibacterial activity are discussed.
在4名健康男性受试者单次静脉注射含64.2% R-差向异构体的替莫西林二钠（1 g纯游离酸）后，对替莫西林侧链差向异构体的药代动力学进行了研究。通过高效液相色谱法测定差向异构体的血浆和尿液浓度。与S-差向异构体相比，R-差向异构体的清除速度快两倍，分布容积大23%，β半衰期短60%。从高效液相色谱数据得出的总替莫西林为中间值。差向异构体药代动力学特性的差异很可能是血浆蛋白结合程度不同所致。在每个血浆样本中，R-差向异构体的游离分数高于（高达两倍）S-差向异构体。在比较从高效液相色谱法和微生物测定数据得出的替莫西林药代动力学参数时，后一种分析得出的值最接近R-差向异构体的值。本文还讨论了其他相对抗菌活性评估中进一步表明R-差向异构体对铜绿假单胞菌NCTC 10701具有更强微生物活性的证据。
