Gastrointestinal transit of amoxicillin modified-release tablets and a placebo tablet including pharmacokinetic assessments of amoxicillin.

BACKGROUND: We have investigated the gastrointestinal transit time of, the influence of food intake on, the disintegration of, and the pharmacokinetics of amoxicillin in a modified-release form. METHODS: Radiolabelled modified-release tablets of amoxicillin and placebo tablets were administered, in an open three-way, randomized, crossover design, as single doses during omeprazole treatment, to six male healthy subjects during fasting and non-fasting conditions. Radioscintigraphic images and plasma samples were obtained. RESULTS: The estimated mean (and range) gastric emptying time of the modified-release tablet after drug administration was 0.3 h (0.1-1.0 h) during fasting conditions, 4.3 h (1.7-5.0 h) after a light breakfast, and 4.9 h (1.9-18.0 h) after a heavy breakfast. The small-intestinal transit time during fasting conditions was 4.7 h (2.9-6.9 h) and was not significantly changed after light or heavy breakfast intake. The relative bioavailability of the modified-release tablet was 55%, compared with a commercially available amoxicillin immediate-release tablet. CONCLUSION: The modified-release tablet of amoxicillin administered postprandially apparently increases the amoxicillin release time in the stomach. The relevance of its use for anti-H. pylori treatment can be questioned.

Absorption, gastrointestinal transit, and tablet erosion of felodipine extended-release (ER) tablets.

The gastrointestinal transit and tablet erosion of felodipine extended release (ER) tablets 10 mg were studied by gamma scintigraphy in eight healthy young males after administration under fasting and nonfasting conditions. Plasma concentrations of felodipine were also measured. Gastric emptying after administration together with food (mean, 3.2 hr) was slower in all subjects compared to emptying under fasting conditions (mean, 0.6 hr). The mean small intestinal transit times for the two study conditions did not differ significantly (5.1 and 4.7 hr, respectively). Tablets did not leave the colon in any subject within 14 hr after administration. Felodipine was shown to be absorbed in the colon, although the major part of the dose was absorbed in the small intestine. The absorption rate of felodipine was related to erosion of the hydrophilic matrix tablet. Tablet erosion and hence drug absorption were slower in the more distal parts of the gastrointestinal tract. Administration together with food did not significantly affect tablet erosion.

Steady-state bioavailability and day-to-day variability of a multiple-unit (CR/ZOK) and a single-unit (OROS) delivery system of metoprolol after once-daily dosing.

Steady-state bioavailability and day-to-day variability of plasma levels were evaluated in 18 healthy male subjects in a crossover study of multiple once-daily administration of two novel oral drug delivery systems of metoprolol and an immediate-release tablet (100 mg metoprolol tartrate). Data were collected over two consecutive 24-hr dosing intervals on treatment days 6 and 7. The two extended-release formulations investigated were metoprolol CR/ZOK (95 mg metoprolol succinate), a multiple-unit system consisting of several hundred membrane-coated delivery units, and metoprolol OROS (95 mg metoprolol fumarate), a single-unit osmotic delivery system. The extended drug release and absorption observed after administration of metoprolol CR/ZOK and metoprolol OROS resulted in similar steady-state plasma concentrations after once-daily dosing. Compared to the immediate-release tablet, they produced considerably lower plasma peaks, three- to fourfold higher trough concentrations, 8-9 hr longer mean residence times, and 20% lower relative bioavailability. Moreover, the two once-daily metoprolol products were found bioequivalent in Cmax and AUC based on 90% confidence intervals for the mean ratio CR/OROS. Repeated plasma concentration measurements on two consecutive 24-hr periods suggested that all three metoprolol treatments produced reproducible and consistent plasma concentrations from day to day at steady state. Assessment of day-to-day variability, however, resulted in significantly lower variation in AUC for the multiple-unit CR/ZOK formulation compared to the single-unit OROS tablet. These results imply that there may be formulation-related differences in the in vivo behavior of the two products despite their being bioequivalent in extent and rate of absorption.