Rodman J H, Flynn P M, Robbins B, Jimenez E, Bardeguez A D, Rodriguez J F, Blanchard S, Fridland A
Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Infect Dis. 1999 Dec;180(6):1844-50. doi: 10.1086/315152.
Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1-infected pregnant women and their newborn infants. Plasma zidovudine and intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.
对28名感染人类免疫缺陷病毒1型的孕妇及其新生儿进行了齐多夫定的全身和细胞内药代动力学研究。在分娩时，对孕妇的系列样本和脐带血中的血浆齐多夫定以及细胞内的齐多夫定单磷酸酯和三磷酸酯浓度进行了测定。脐带血中较高的齐多夫定水平与较低的母体齐多夫定清除率和较长的输注时间相关。母体血液（1556和67 fmol/106细胞）和脐带血（1464和70 fmol/106细胞）中齐多夫定单磷酸酯和三磷酸酯的中位数水平相似，但差异很大。齐多夫定的个体间药代动力学变异性很大，但静脉治疗可提供与高抗病毒活性一致的血浆浓度和细胞内齐多夫定三磷酸酯水平。脐带血中大量的细胞内齐多夫定三磷酸酯为齐多夫定在减少垂直传播方面的临床成功提供了解释。现在可以评估更简单的齐多夫定口服方案在实现这些与高效肠外治疗相关的药理学终点方面的能力。
