Pharmacokinetics of Zidovudine Phosphorylation in Human Immunodeficiency Virus-Positive Thai Patients and Healthy Volunteers

ABSTRACT We assessed the pharmacokinetics of zidovudine (ZDV) in plasma and intracellular ZDV phosphate anabolites in peripheral blood mononuclear cells in Thai human immunodeficiency virus (HIV) type 1-infected patients and healthy volunteers. The plasma ZDV area under the concentration-time curve from 0 to 6 h (AUC0–6) was similar in patients and healthy volunteers (32.77 and 22.77 μmol/liter · h, respectively; confidence interval, −3.37 to 19.92). Although the concentration of ZDV triphosphate (ZDVTP) was similar in the two groups, the ZDV monophosphate (ZDVMP) AUC0–6 was significantly greater in HIV patients (1.12 pmol/106 cells) than in healthy volunteers (0.15 pmol/106 cells). In agreement with previously published data obtained with Caucasians, the significant difference in intracellular phosphorylation in Thai volunteers and HIV patients is primarily due to ZDVMP. Comparing the data from this study with the data obtained with Caucasians suggests no marked ethnic differences in ZDV phosphorylation.

[1]  B. Jacobsson,et al.  Decrease in thymidylate kinase activity in peripheral blood mononuclear cells from HIV-infected individuals. , 1998, Biochemical pharmacology.

[2]  B. Sha,et al.  Administration of zidovudine during late pregnancy and delivery to prevent perinatal HIV transmission--Thailand, 1996-1998. , 1998, MMWR. Morbidity and mortality weekly report.

[3]  A. Breckenridge,et al.  The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites , 1996, AIDS.

[4]  J. Gambertoglio,et al.  Zidovudine phosphorylation after short‐term and long‐term therapy with zidovudine in patients infected with the human immunodeficiency virus , 1996, Clinical pharmacology and therapeutics.

[5]  D. Back,et al.  Metabolism of Zidovudine. , 1995, General pharmacology.

[6]  D. Back,et al.  Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells. , 1994, British journal of clinical pharmacology.

[7]  N. Beeching,et al.  Zidovudine phosphorylation in HIV‐infected patients and seronegative volunteers , 1994, AIDS.

[8]  A. Pesce,et al.  Correlates of zidovudine phosphorylation with markers of HIV disease progression and drug toxicity , 1994, AIDS.

[9]  A. Pesce,et al.  Pharmacokinetics of zidovudine phosphorylation in patients infected with the human immunodeficiency virus. , 1992, Therapeutic drug monitoring.

[10]  B. Jacobsson,et al.  Intracellular metabolism of 3'-azidothymidine in isolated human peripheral blood mononuclear cells. , 1991, AIDS research and human retroviruses.

[11]  Honghao Zhou,et al.  Ethnic Differences in Drug Disposition and Responsiveness , 1991, Clinical pharmacokinetics.

[12]  A. Pesce,et al.  In Vitro Measurement of Phosphorylated Zidovudine in Peripheral Blood Leucocytes , 1990, Therapeutic drug monitoring.

[13]  M. Clerici,et al.  Detection of three distinct patterns of T helper cell dysfunction in asymptomatic, human immunodeficiency virus-seropositive patients. Independence of CD4+ cell numbers and clinical staging. , 1989, The Journal of clinical investigation.

[14]  K. Weinhold,et al.  3'-Azido-3'-deoxythymidine triphosphate as an inhibitor and substrate of purified human immunodeficiency virus reverse transcriptase , 1987, Antimicrobial Agents and Chemotherapy.

[15]  Broder,et al.  Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Chokephaibulkit,et al.  From the Centers for Disease Control and Prevention. Administration of zidovudine during late pregnancy and delivery to prevent perinatal HIV transmission--Thailand, 1996-1998. , 1998, JAMA.