Intracellular pharmacokinetic study of zidovudine and its phosphorylated metabolites.
Level 4 - case-series / case-control
Single-arm pharmacokinetic study in healthy human volunteers without a control group
PubMed 27006900 · doi:10.1016/j.apsb.2015.10.002
What was done
Twelve healthy Chinese male volunteers received a single oral dose of 600 mg zidovudine (AZT). Blood samples were collected before dosing and across 12 time points up to 10 hours post-dose. Peripheral blood mononuclear cells (hPBMCs) were isolated to measure intracellular concentrations of AZT, AZT monophosphate (AZT-MP), AZT diphosphate (AZT-DP), and AZT triphosphate (AZT-TP). Plasma was analyzed concurrently for AZT pharmacokinetics.
What was found
- Plasma AZT peaked within 0.583 h with an elimination half-life (t 1/2) of 2.022 h. - Intracellular peak times were 1.083 h for AZT, 1.500 h for AZT-MP, 1.417 h for AZT-DP, and 1.583 h for AZT-TP. - Intracellular elimination half-lives were 13.428 h for AZT-MP, 8.285 h for AZT-DP, and 4.240 h for AZT-TP. - Phosphorylated metabolites in plasma were not quantifiable.
Why it matters
This study provides human in vivo intracellular pharmacokinetic parameters for zidovudine, demonstrating that the active antiviral metabolite (AZT-TP) persists in target mononuclear cells longer than parent zidovudine in plasma.
Limits
Small sample size (n = 12) restricted to healthy Chinese males; does not capture pharmacokinetics in females or HIV-infected individuals. Evaluated only a single dose rather than steady-state clinical dosing. The 10-hour sampling period was relatively brief given the 13.4-hour intracellular half-life of AZT-MP.
Cited by
- supports Inside cells, AZT is phosphorylated into AZT triphosphate, which acts as an inhibitor of reverse transcriptase.