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Clinical Report |
HIBA L. TAPPOUNI, PHARM.D., is Principal Clinical Research Scientist, Psychiatry, GlaxoSmithKline, Research Triangle Park, NC; at the time of writing, she was Drug Development Fellow, Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina (UNC), Chapel Hill. JOHN C. RUBLEIN, PHARM.D., is Senior Clinical Science Manager, Abbott Pharmaceuticals, Abbott Park, IL; at the time of writing, he was Clinical Specialist, Infectious Diseases, UNC Hospitals, Chapel Hill. BRIAN J. DONOVAN, PHARM.D., is Clinical Scientific Director, Cubist Pharmaceuticals, Lexington, MA; at the time of writing, he was Specialty Resident, Infectious Diseases Pharmacotherapy, UNC, Chapel Hill. STEPHANIE B. HOLLOWELL, PHARM.D., is Clinical Pharmacist, Chippenham Johnston-Willis Medical Center, Richmond, VA. HSIAO-CHUAN TIEN, PH.D., is Senior Statistician, Department of Biostatistics, School of Public Health, UNC, Chapel Hill. SHERENE S. MIN, M.D., is Director, Clinical Pharmacology Discovery Medicine, GlaxoSmithKline. DICKENS THEODORE, M.D., is Director, Clinical Development, GlaxoSmithKline; at the time of writing, he was Senior Research Physician, GlaxoSmithKline. NASER L. REZK, M.S., is Assistant Professor, Division of Pharmacotherapy and Experimental Therapeutics; PHILIP C. SMITH, PH.D., is Associate Professor, Division of Molecular Pharmaceutics; MELANIE N. TALLMAN, PHARM.D., is Graduate Student, Division of Molecular Pharmaceutics; RALPH H. RAASCH, PHARM.D., is Associate Professor, Division of Pharmacotherapy and Experimental Therapeutics; and ANGELA D. M. KASHUBA, PHARM.D., is Associate Professor, Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, UNC.
Address correspondence to Dr. Kashuba at the School of Pharmacy, CB7360, University of North Carolina, Chapel Hill, NC 27599-7360 (akashuba{at}unc.edu).
Methods. Fourteen men and women age 18–55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography.
Results. The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg · hr/L (95% confidence interval [CI], 21.9–41.1 mg · hr/L) to 19.7 mg · hr/L (95% CI, 14.6–26.8 mg · hr/L) or 16.0 mg · hr/L (95% CI, 11.8–21.7 mg · hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg · hr/L (95% CI, 21.9–41.1 mg · hr/L) to 46.6 mg · hr/L (95% CI, 34.0–63.8 mg · hr/L), but it did not significantly affect mean omeprazole concentrations (p
Conclusion. The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.
Index terms: Antiretroviral agents; Blood levels; Dosage; Drug interactions; Gastrointestinal drugs; HIV infections; Indinavir; Omeprazole; Pharmacokinetics; Ritonavir
Purpose. The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. 
0.02).
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