Effervescent and standard formulations of ranitidine - a comparison of their pharmacokinetics and pharmacology

Watson, Rgp; Johnston, B. T.; Tham, T. C. K.; Kersey, Kathryn

doi:10.1016/0016-5085(95)23680-5

Cited by 2 publications

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“…Although no statistical comparison between the two test treatments was made, ranitidine appeared to result in a larger decrease in plasma APV exposure than MAALOX TC. Given that ranitidine does not have a chelation effect but results in a more durable increase in gastric pH than MAALOX TC (11), the mechanism of these interactions was likely related to increased gastric pH, although a component of phosphate binding by the antacid cannot be ruled out. Increased gastric pH has also decreased the absorption of the HIV protease inhibitors atazanavir (2) and indinavir (3) but to a much greater magnitude (Ͼ80% decrease in plasma atazanavir and indinavir exposures) than that observed for FPV.…”

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Effect of Antacids and Ranitidine on the Single-Dose Pharmacokinetics of Fosamprenavir

Ford

Wire

Lou

et al. 2005

Antimicrob Agents Chemother

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Single doses of MAALOX TC and ranitidine were administered separately with 1,400 mg of fosamprenavir (FPV). MAALOX TC decreased the area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (C max ) by 35%; the plasma APV concentration at 12 h (C 12 ) increased by 14%. Ranitidine at 300 mg decreased the AUC 0-24 for plasma APV by 30% and C max by 51%; C 12 was unchanged. FPV may be coadministered with antacids without concern and without separation in dosing; however, caution is recommended when FPV is coadministered with histamine 2 -receptor antagonists or proton pump inhibitors.Fosamprenavir (FPV, GW433908) has been approved for treatment of human immunodeficiency virus (HIV)-infected adult patients. FPV, a phosphoester prodrug, is rapidly and extensively hydrolyzed to the HIV protease inhibitor amprenavir (APV) during absorption, with minimal systemic FPV exposure (12).Due to the chemical properties of FPV, an interaction with both antacids and histamine 2 -receptor antagonists is possible. FPV exhibits pH-dependent solubility, with maximal solubility at pH 3.3 and reduced solubility at higher pHs (5). The phosphate group on FPV could bind to the metal cations contained in antacids, which could either alter solubility or prevent presystemic conversion of FPV to APV. This study assessed the effects of antacids and ranitidine on single-dose plasma APV pharmacokinetics following administration of FPV.This single-dose, open, randomized, three-way balanced crossover study included administration of 1,400 mg of FPV alone, 1,400 mg of FPV immediately following 30 ml of oral antacid (MAALOX TC; Novartis Consumer Health), 1,800 mg of magnesium hydroxide and 3,600 mg of aluminum hydroxide dried gel (2,754 mg of aluminum hydroxide), and 1,400 mg of FPV 1 h after 300 mg of ranitidine. There was a 4-to 7-day washout between each treatment. Subjects fasted overnight, continuing until 4 h after dosing. Water was permitted ad libitum during the overnight fast. The study drug was administered with 180 ml of water, and additional water was permitted ad libitum from 2 h after dosing. The container in which MAALOX TC was administered was rinsed, and the water was consumed. Blood samples were collected in sodium citratecontaining tubes (Vacutainers; Becton-Dickinson) at 0, 0. 25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 h after dosing. Prior to analysis, plasma was stored at or below 30°C, at which temperature stability has been confirmed for 32 months. Plasma APV and FPV concentrations were measured within 4 months of initial dosing using a validated high-performance liquid chromatography assay with tandem mass spectrometric detection following solid-phase extraction (the linear range for APV was 10 to 10,000 ng/ml, and that for FPV was 5 to 1,000 ng/ml). For APV, intra-assay precision, interassay precision (percent coefficient of variation), and accuracy (percent bias) were Յ13.83, Յ2.57, and Յ10.47, respectively. Ph...

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