Abstract
A total of 71 HIV-negative healthy adults were randomized to 1 of 6 regimens to receive lopinavir/ritonavir tablets 400/100 mg twice daily (bid) or 800/200 mg once daily (qd) or atazanavir 300 mg + ritonavir 100 mg qd from study days 1 to 15 with a moderate-fat meal. One hour before breakfast, either omeprazole 40 mg qd was administered on study days 11 through 15, or a single dose of ranitidine 150 mg was administered on study day 11. Lopinavir, atazanavir, and ritonavir pharmacokinetics were determined on study days 10, 11, and 15 and compared using point estimates and 90% confidence intervals (CIs). The point estimates for lopinavir Cmax and AUCtau were in the range of 0.92 to 1.08, with 90% CI contained within the range of 0.80 to 1.25 after coadministration of omeprazole or ranitidine. The point estimates for atazanavir Cmax and AUCtau were decreased by 48% to 62% with the upper bound of the 90% CI <or=0.55 after coadministration of omeprazole or ranitidine. The results indicated that lopinavir bioavailability was not affected by the coadministration of omeprazole or ranitidine. In contrast, atazanavir bioavailability was decreased by 48% to 62% when coadministered with ritonavir and either omeprazole or ranitidine.
Publication types
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Clinical Trial, Phase I
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Randomized Controlled Trial
MeSH terms
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Adult
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Anti-HIV Agents / administration & dosage
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Anti-HIV Agents / blood
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Anti-HIV Agents / pharmacokinetics
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Anti-Ulcer Agents / administration & dosage
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Anti-Ulcer Agents / adverse effects
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Anti-Ulcer Agents / pharmacokinetics
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Area Under Curve
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Atazanavir Sulfate
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Biological Availability
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Dose-Response Relationship, Drug
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Drug Interactions
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Female
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HIV Protease Inhibitors / administration & dosage
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HIV Protease Inhibitors / blood
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HIV Protease Inhibitors / pharmacokinetics
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Histamine H2 Antagonists / administration & dosage
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Histamine H2 Antagonists / adverse effects
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Histamine H2 Antagonists / pharmacokinetics
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Humans
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Lopinavir
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Male
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Middle Aged
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Oligopeptides / administration & dosage
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Oligopeptides / blood
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Oligopeptides / pharmacokinetics*
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Omeprazole / administration & dosage
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Omeprazole / adverse effects
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Omeprazole / pharmacokinetics*
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Pyridines / administration & dosage
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Pyridines / blood
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Pyridines / pharmacokinetics*
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Pyrimidinones / administration & dosage
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Pyrimidinones / blood
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Pyrimidinones / pharmacokinetics*
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Ranitidine / administration & dosage
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Ranitidine / adverse effects
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Ranitidine / pharmacokinetics*
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Ritonavir / administration & dosage
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Ritonavir / blood
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Ritonavir / pharmacokinetics*
Substances
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Anti-HIV Agents
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Anti-Ulcer Agents
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HIV Protease Inhibitors
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Histamine H2 Antagonists
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Oligopeptides
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Pyridines
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Pyrimidinones
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Lopinavir
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Atazanavir Sulfate
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Ranitidine
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Omeprazole
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Ritonavir