Strategies for control of zidovudine concentrations in serum.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Strategies for control of zidovudine concentrations in serum.

Antimicrob Agents Chemother. 1995 Dec;39(12):2792-7. Unique Identifier : AIDSLINE MED/96161301
Noormohamed SE; Henry WK; Rhame FS; Balfour HH Jr; Fletcher CV; Department of Pharmacy Practice, University of Minnesota Health; Sciences Center, Minneapolis 55455, USA.

Abstract: There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of pharmacokinetic parameters for zidovudine derived from sparse serum concentration data obtained in an outpatient setting. Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentrations determinations obtained on two different clinic visits, 2 to 38 days apart. Zidovudine concentrations were measured by radioimmunoassay. A one-compartment oral absorption model was used to describe zidovudine disposition. Three different approaches were used to estimate pharmacokinetic parameters: Bayesian estimation with one or two concentrations and least squares with one concentration. The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and compared with predictions using standard fixed or weight-adjusted parameters. Estimated pharmacokinetic parameters for zidovudine were consistent with literature values; there was no statistically significant difference among the parameters calculated with the three estimation strategies. Absorptive phase concentrations were poorly predicted by all methods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%). Predictive ability for concentrations obtained in the elimination phase was strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%. Bayesian and least-squares estimated parameters were statistically better than fixed-parameter values for predicting concentrations in the elimination phase. These observations provide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug interaction, and conduct concentration-controlled clinical trials.

Keywords: Adolescence Adult Antiviral Agents/*BLOOD/PHARMACOKINETICS Bayes Theorem Human HIV Infections/*BLOOD Middle Age Models, Biological Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Zidovudine/*BLOOD/PHARMACOKINETICS CLINICAL TRIAL JOURNAL ARTICLE

960630
M9660732

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