Effect of pregnancy, mode of administration and neonatal age on the pharmacokinetics of zalcitabine (2', 3'-dideoxycytidine) in the pigtailed macaque (Macaca nemestrina)

The Journal of Antimicrobial Chemotherapy
T TuntlandJ D Unadkat

Abstract

Our objective was to determine the effect of pregnancy, mode of administration and neonatal age on the pharmacokinetics of the anti-HIV drug zalcitabine (2',3'-dideoxycytidine; ddC) in the pigtailed macaque (Macaca nemestrina). Zalcitabine was administered as an i.v. bolus dose to pregnant dams (n = 3) at term and at 6 weeks post-partum. No significant differences were found between the pre- and post-partum systemic plasma clearance, steady-state volume of distribution or terminal plasma half-life of zalcitabine, indicating that pregnancy does not affect the pharmacokinetics of the drug in the macaque. The observed maternal plasma, fetal plasma and amniotic fluid concentration-time profiles were compared with profiles that were simulated using pharmacokinetic parameter estimates obtained in an earlier constant i.v. infusion study in pregnant macaques. The fetal:maternal ratio of the area under the simulated zalcitabine plasma concentration-time profile after an i.v. bolus dose (0.58) was close to the earlier observed fetal:maternal steady-state plasma concentration ratio after i.v. infusion of the drug (0.58 +/- 0.05). The excellent agreement between observed and simulated fetal:maternal ratio of zalcitabine demonstrates that t...Continue Reading

Citations

Feb 12, 2013·Bioanalysis·Robin DiFrancescoGene D Morse
Aug 28, 2001·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·G P Taylor, N Low-Beer

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