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Ileectomy-induced Bile Overaccumulation in Mouse Intestine
Published on: August 21, 2017
Decrease in gastrointestinal absorption of roxithromycin in bile duct cannulated rats due to depletion of bile salts
Joo Hyun Lee1, Young Ju Park, Ju-Hee Oh
1Division of Biopharmaceutics, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea.
Biopharmaceutics & Drug Disposition
|May 25, 2013
Summary
Bile salts are crucial for roxithromycin absorption in rats. Depleting bile significantly reduced drug levels, but adding bile salts restored them, suggesting dosage adjustments for patients with bile deficiency.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Gastrointestinal Physiology
Background:
- Bile salts play a vital role in the absorption of many orally administered drugs.
- The plasma second peak phenomenon, indicative of enterohepatic circulation, can influence drug bioavailability.
- Roxithromycin is a macrolide antibiotic whose absorption may be affected by gastrointestinal conditions.
Purpose of the Study:
- To investigate the impact of bile salts on the gastrointestinal absorption of roxithromycin in a rat model.
- To examine the effect of bile depletion and repletion on roxithromycin's plasma concentration-time profile, including the second peak phenomenon.
Main Methods:
- Pharmacokinetic analysis of roxithromycin following oral administration (20 mg/kg) in three groups of rats: control, bile duct cannulated (BDC), and bile salt co-administered bile duct cannulated (BSBDC).
- Measurement of key pharmacokinetic parameters including total area under the plasma concentration-time curve (AUC0-∞) and peak plasma concentration (Cmax).
- In vitro assessment of roxithromycin solubility in the presence of sodium taurocholate.
Main Results:
- Bile duct cannulation in rats led to significantly reduced AUC0-∞ (0.572-fold) and Cmax (0.412-fold) for roxithromycin compared to controls, indicating impaired absorption.
- Co-administration of bile salts in BDC rats restored AUC0-∞ to 0.831-fold and Cmax to 0.828-fold of control values, suggesting bile depletion was responsible for decreased absorption.
- Roxithromycin solubility increased 3.09-fold at 30 mm sodium taurocholate, supporting the role of bile salts in enhancing drug dissolution and absorption.
Conclusions:
- Bile depletion significantly impairs the gastrointestinal absorption and plasma concentration of roxithromycin in rats.
- Supplementation with bile salts can mitigate the negative effects of bile deficiency on roxithromycin pharmacokinetics.
- Findings suggest potential need for adjusting roxithromycin dosage in humans with bile deficiency or during high-fat diets, pending extrapolation of rat data.
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