Document Detail

Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats.
MedLine Citation:
PMID:  19505375     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: This study was to investigate the effect of hesperidin, an antioxidant, on the bioavailability and pharmacokinetics of diltiazem and its active major metabolite, desacetyldiltiazem, in rats. METHODS: A single dose of diltiazem was administered orally (15 mg/kg) in the presence or absence of hesperidin (1, 5 or 15 mg/kg), which was administered 30 min before diltiazem. KEY FINDINGS: Compared with the control group (given diltiazem alone), hesperidin (5 or 15 mg/kg) significantly altered the pharmacokinetic parameters of diltiazem, except for 1 mg/kg hesperidin. The area under the plasma concentration-time curve from time 0 h to infinity (AUC(0-infinity)) was significantly (5 mg/kg, P < 0.05; 15 mg/kg, P < 0.01) increased by 48.9-65.3% and the peak plasma concentration (C(max)) was significantly (P < 0.05) increased by 46.7-62.4% in the presence of hesperidin (5 or 15 mg/kg). Consequently, the absolute bioavailability (F) of diltiazem with hesperidin was significantly (5 mg/kg, P < 0.05; 15 mg/kg, P < 0.01) higher than that in the control group. Hesperidin (5 or 15 mg/kg) significantly (P < 0.05) increased the AUC(0-infinity) and 15 mg/kg of hesperidin significantly (P < 0.05) increased the C(max) of desacetyldiltiazem. However, the metabolite-parent ratio (MR) of desacetyldiltiazem was not significantly changed in the presence of hesperidin. CONCLUSIONS: Hesperidin significantly enhanced the oral bioavailability of diltiazem in rats. It might be considered that hesperidin increased the intestinal absorption and reduced the first-pass metabolism of diltiazem in the intestine and in the liver via an inhibition of cytochrome P450 3A or P-glycoprotein.
Young-Ah Cho; Dong-Hyun Choi; Jun-Shik Choi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  61     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-09     Completed Date:  2009-08-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  825-9     Citation Subset:  IM    
BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
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MeSH Terms
Administration, Oral
Antioxidants / pharmacology*
Area Under Curve
Biological Availability
Calcium Channel Blockers / administration & dosage,  pharmacokinetics*
Chromatography, High Pressure Liquid
Diltiazem / administration & dosage,  analogs & derivatives*,  metabolism,  pharmacokinetics*
Dose-Response Relationship, Drug
Drug Interactions
Hesperidin / pharmacology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antioxidants; 0/Calcium Channel Blockers; 42399-40-6/deacetyldiltiazem; 42399-41-7/Diltiazem; 520-26-3/Hesperidin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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