Influence of a Fat-Rich Meal on Bioavailability of Extended-Release and Immediate-Release Propiverine
| Autor: | Werner Siegmund, K. Richter, Frieder Schnabel, Cornelia Feustel, Wilhelm Kirch, Joachim Siegert |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Metabolic Clearance Rate Chemistry Pharmaceutical Metabolite Biological Availability Muscarinic Antagonists Pharmacology Benzilates Models Biological Intestinal absorption Food-Drug Interactions Young Adult chemistry.chemical_compound Germany Internal medicine medicine Humans Pharmacology (medical) Biotransformation Analysis of Variance Meal CYP3A4 Chemistry Antagonist Fasting Middle Aged Postprandial Period Dietary Fats Small intestine Bioavailability medicine.anatomical_structure Endocrinology Intestinal Absorption Area Under Curve Delayed-Action Preparations Female Propiverine Oxidation-Reduction Half-Life medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 52:681-690 |
| ISSN: | 0091-2700 |
| Popis: | The muscarinic receptor antagonist propiverine is unique insofar as extended-release (ER) tablets are of higher bioavailability than immediate-release (IR) tablets; this is caused by lower "first-pass" elimination of propiverine via CYP3A4 and efflux transporters in the distal small intestine and colon. Food may influence gastrointestinal transiting and, in turn, may affect regional absorption of propiverine IR and ER. Therefore, food effects on disposition of 30 mg IR and 45 mg ER were measured in a randomized, open, 4-period interaction study in 24 healthy participants. In fasting participants, ER had higher bioavailability than IR (F(rel) = 169%, P = .03). Fat-rich meal did not change the disposition of ER markedly (AUC(0-∞) ratio, 1.00 [90% confidence interval (CI), 0.90-1.11], C(max) ratio, 0.97 [0.87-1.09]). However, C(max) and renal A(e) of the major N-oxidized metabolite (M-5) significantly increased, whereas t(1/2) decreased. By eating a fat-rich meal before administration, the differences in absorption of IR and ER were nearly abolished (AUC(0-∞) ratio for propiverine, 1.12 [90% CI, 0.95-1.33]; AUC(0-∞) ratio for M-5, 0.89 [0.82-0.95]). In conclusion, propiverine ER has higher bioavailability than IR and no positive food effect because it reaches, independently of food, intestinal absorption areas with lower metabolism and efflux transport, which results in constant absorption rates. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text