Intravascular distribution of zidovudine: Role of plasma proteins and whole blood components

doi:10.1016/0166-3542(93)90032-E

Antiviral Research

Volume 21, Issue 3, July 1993, Pages 267-280

https://doi.org/10.1016/0166-3542(93)90032-E Get rights and content

Abstract

Knowledge of drug protein-binding and blood cell partitioning may be important for evaluating the pharmacokinetic parameters of zidovudine, particularly because of its intracellular site of action and potential to induce side effects. Equilibrium dialysis studies of zidovudine were performed over 2 h to identify the extent and site of binding. Zidovudine was added to anticoagulated whole blood to study blood cell distribution over a 24 h period at 37°C and at 21°C. Concurrent plasma and whole blood samples were determined at various time-points and blood partitioning was determined by application of a mass balance equation. All samples were analyzed using radioimmunoassay. The free fraction of zidovudine at a concentration of 500 ng/ml (1.7 μM) was 0.77 ± 0.05 in plasma, 0.78 ± 0.03 in serum, 0.88 ± 0.03 in 4 g/dl albumin solution, and 1.0 in 100 mg/dl α1-acid glycoprotein solution. A free fraction of 0.72 ± 0.10 was observed in plasma from HIV-infected patients with zidovudine concentrations ranging from 16 to 91 ng/ml. Zidovudine equilibration between plasma and blood cells occurred rapidly, being complete within 10 min. After equilibrium was complete, the mean whole blood:plasma ratio was 0.86 ± 0.02 and 0.80 ± 0.04 (P = 0.20) and mean blood cell Partitioning ratio, [cell]/[plasma-free], was 0.85 ± 0.06 and 0.66 ± 0.14 (P = 0.25) for studies at 37°C and 21°C, respectively. The partitioning ratio was relatively consistent over the study period, suggesting no accumulation in blood cells. These results suggest that zidovudine binds to a small extent primarily to albumin. The free concentration equilibrates readily between blood cells and plasma independent of concentration and without signs of accumulation.

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Research articleIntravascular distribution of zidovudine: Role of plasma proteins and whole blood components

Abstract

J. Pharm. Sci.

J. Chromatogr

Anal. Biochem.

J. Biol. Chem.

Errors in interpretation of data from equilibrium dialysis protein-binding experiments

Res. Commun. Chem. Pathol. Pharmacol.

Pharmacokinetics and bioavailability of zidovudine in humans

Am. J. Med.

C14-Ribavirin: distribution and pharmacokinetic studies in rats, baboons and man

Pyrimidine dideoxyribonucleosides: selectivity of penetration into cerebrospinal fluid

J. Pharm. Exper. Ther.

Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase

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Clin. Pharmacol. Ther.

Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome

New Engl. J. Med.

Inhibition of bone marrow myelopoiesis and erythropoiesis in vitro by anti-retroviral nucleoside derivatives

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Research article
Intravascular distribution of zidovudine: Role of plasma proteins and whole blood components