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Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption.
- Source :
-
Pharmaceutical research [Pharm Res] 2017 Mar; Vol. 34 (3), pp. 619-628. Date of Electronic Publication: 2016 Dec 27. - Publication Year :
- 2017
-
Abstract
- Purpose: Clinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria.<br />Methods: In this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule.<br />Results: Pretreatment with rabeprazole resulted in significant reductions in atazanavir C <subscript>max</subscript> (p < 0.01) and AUC <subscript>0-last</subscript> (p < 0.001) (71 and 70%, respectively), and modest decreases in ritonavir C <subscript>max</subscript> and AUC <subscript>last</subscript> (p < 0.01) (40% and 41%, respectively). The addition of betaine HCl restored 13% of ATV C <subscript>max</subscript> and 12% of AUC <subscript>last</subscript> lost due to rabeprazole.<br />Conclusions: The co-administration of rabeprazole with atazanavir resulted in significant decreases in atazanavir exposure. The addition of betaine HCl did not sufficiently mitigate the loss of ATV exposure observed during RAB-induced hypochlorhydria. Meal effects lead to a marked difference in the outcome of betaine HCl on atazanavir exposure than we previously reported for dasatanib under fasting conditions.
- Subjects :
- Absorption, Physiological
Achlorhydria chemically induced
Achlorhydria prevention & control
Administration, Oral
Adult
Atazanavir Sulfate administration & dosage
Betaine administration & dosage
Cross-Over Studies
Drug Interactions
Female
HIV Protease Inhibitors administration & dosage
Humans
Male
Middle Aged
Proton Pump Inhibitors adverse effects
Rabeprazole adverse effects
Ritonavir administration & dosage
Young Adult
Achlorhydria metabolism
Atazanavir Sulfate pharmacokinetics
Food-Drug Interactions
HIV Protease Inhibitors pharmacokinetics
Proton Pump Inhibitors pharmacokinetics
Rabeprazole pharmacokinetics
Ritonavir pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 34
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 28028768
- Full Text :
- https://doi.org/10.1007/s11095-016-2090-2