title: Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites.
abstract: Zidovudine (AZT), the first drug approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection, is metabolized in the host cells to 5'-AZT triphosphate (AZT-TP) which inhibits HIV reverse transcriptase. As the pharmacokinetics of AZT and its phosphorylated metabolites in human peripheral blood mononuclear cells (hPBMCs) is limited, the aim of this study was to determine the pharmacokinetic parameters of AZT and its phosphorylated metabolites in hPBMCs from 12 healthy Chinese male subjects after a single oral dose of 600 mg of AZT. Blood samples were collected prior to drug administration, then at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 10 h after drug administration. Mononuclear cells collected by Ficoll-Hypaque density gradient centrifugation were used for determination of AZT and metabolites [AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP) and AZT-TP] and the plasma was used to evaluate the pharmacokinetics of AZT. Plasma concentration of AZT peaked within 0.583 h and intracellular concentrations of AZT, AZT-MP, AZT-DP and AZT-TP peaked within 1.083, 1.500, 1.417 and 1.583 h, respectively. AZT in plasma was eliminated rapidly with t 1/2 of 2.022 h, and AZT-MP, AZT-DP and AZT-TP were eliminated with t 1/2 of 13.428, 8.285 and 4.240 h, respectively. The plasma concentration of the phosphorylated metabolites was not quantifiable.
authors.affiliation: Medical College, Hunan Normal University, Changsha 410006, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Mu
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Xingling
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Sanwang
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Feifan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Medical College, Hunan Normal University, Changsha 410006, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xie
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.affiliation: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
keywords: Intracellular kinetic; LC–MS/MS; Metabolites; Pharmacokinetics; Phosphates; Zidovudine; hPBMCs