Alteration of zidovudine pharmacokinetics by probenecid in patients with AIDS or AIDS-related complex. NLM AIDSLINE Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

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Alteration of zidovudine pharmacokinetics by probenecid in patients with AIDS or AIDS-related complex.

Clin Pharmacol Ther. 1989 Nov;46(5):494-500. Unique Identifier : AIDSLINE MED/90059071
de Miranda P; Good SS; Yarchoan R; Thomas RV; Blum MR; Myers CE; Broder S; Wellcome Research Laboratories, Research Triangle Park, NC.

Abstract: The anti-human immunodeficiency virus drug zidovudine is metabolized extensively in human beings to the 5'-glucuronide (GAZT) and is cleared rapidly, resulting in a short half-life and the need for frequent dosing. This study explores whether probenecid, which is also metabolized by glucuronidation, reduces zidovudine clearance when zidovudine is administered orally to patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The mean zidovudine plasma levels were significantly higher after concurrent administration of probenecid than in its absence, resulting in a twofold increase in the mean AUC, a corresponding decline in the apparent total clearance, and a prolongation in the mean half-life. Similar alterations were observed in GAZT disposition. There was a marked reduction in the urinary excretion ratio of GAZT to zidovudine and a decline in the renal clearance of GAZT after probenecid coadministration. Probenecid inhibits zidovudine glucuronidation and renal excretion of GAZT.
Keywords: Acquired Immunodeficiency Syndrome/*METABOLISM Adult AIDS-Related Complex/*METABOLISM Drug Interactions Drug Therapy, Combination Half-Life Human Male Middle Age Probenecid/*PHARMACOLOGY/PHARMACOKINETICS Regression Analysis Zidovudine/ANALOGS & DERIVATIVES/BLOOD/*PHARMACOKINETICS/URINE JOURNAL ARTICLEKWDacquiredimmunodeficiencysyndrome/KWDmetabolismadultaids-relatedcomplex/KWDmetabolismdruginteractionsdrugtherapy,combinationhalf-lifehumanmalemiddleageprobenecid/KWDpharmacology/pharmacokineticsregressionanalysiszidovudine/analogs&derivatives/blood/KWDpharmacokinetics/urinejournalarticle
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