Delavirdine malabsorption in HIV-infected subjects with spontaneous gastric hypoacidity.
To determine the impact of gastric hypoacidity and acidic beverages on delavirdine mesylate pharmacokinetics in HIV-infected subjects, matched subjects with (n = 11) and without (n = 10) gastric hypoacidity received delavirdine 400 mg tid with either water or an acidic beverage (usually orange juice). The pharmacokinetics of delavirdine and its N-desalkyl metabolite were determined over 8 hours after 14 days of each treatment. Gastric pH was measured at baseline and during each pharmacokinetic evaluation. Delavirdine exposure (Cmax, AUC0-->8 h, and Cmin) was approximately 50% lower and the extent of delavirdine metabolism was higher in subjects with gastric hypoacidity. Orange juice produced a lower mean gastric pH compared to water and increased delavirdine absorption by 50% to 70% in subjects with gastric hypoacidity. However, orange juice had a marginal impact on delavirdine exposure in subjects without gastric hypoacidity. HIV-infected subjects with gastric hypoacidity significantly malabsorb delavirdine. Delavirdine administration with acidic beverages improves, but dose not normalize, absorption in these subjects.
Shelton
Mark J
MJ
GlaxoSmithKline, Five Moore Drive, P.O. Box 1398, Research Triangle Park, NC 27709, USA.
Hewitt
Ross G
RG
Adams
John M
JM
Cox
Steve R
SR
Chambers
James H
JH
Morse
Gene D
GD
D000328:Adult; D019540:Area Under Curve; D001628:Beverages; D002957:Citrus; D018592:Cross-Over Studies; D020008:Delavirdine / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male
D020008:Delavirdine