Pharmacokinetics of 8 mg galantamine hydrobromide prolonged-release capsules under fed and fasting conditions

Abstract

Objective: The objective of the study was to determine the pharmacokinetics of 8 mg galantamine prolonged-release capsules under fed and fasting conditions. Materials and Methods: A randomized, open-label, single-dose, two-treatment, two-period, two-sequence, parallel design of the administration of 8 mg galantamine hydrobromide prolonged-release capsules under fed and fasting conditions in 52 healthy Thai volunteers. Each subject was randomly assigned to receive a single oral dose of galantamine under fed or fasting conditions with a 7-day washout period. Blood samples were collected at 0.0, 1.0, 2.0, 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 9.0, 10.0, 12.0, 24.0, 36.0, and 48.0 h following drug administration. Liquid chromatography–tandem mass spectrometry was used for the quantitation of galantamine in plasma. Pharmacokinetic parameters were analyzed including Cmax, Tmax, T1/2, ke, AUC0-48h, and AUC0-inf. Results: A total of 46 subjects completed the present study. The mean Cmax (range) values were 41.95 ± 10.05 (24.86–61.88) ng/mL and 25.96 ± 4.18 (18.82–33.60) ng/mL, and the mean AUC0-48h values were 599.45 ± 159.54 ng.h/mL and 503.47 ± 79.62 ng.h/mL under fed and fasting conditions, respectively. The mean AUC0-inf values under fed and fasting conditions were 620.89 ± 173.95 ng.h/mL and 527.43 ± 83.97 ng.h/mL, respectively. The mean (range) Tmax value under fed conditions was 5.70 ± 1.36 (4–8) h and under fasting conditions was 5.61 ± 1.71 (1–8) h, which were not significantly different (P = 0.10; Mann–Whitney U-test). The Cmax was 59% higher under fed conditions, with a treatment condition ratio of 1.5906, which was significantly different. Conclusions: High-fat and high-calorie foods increased the maximum concentration (Cmax) and the extent of absorption (AUC) but did not affect the galantamine absorption rate (Tmax).