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Effects of morin pretreatment on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem in rats

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An Erratum to this article was published on 01 October 2006

Abstract

The purpose of this study was to investigate the effect of morin, a flavonoid, on the pharmaco-kinetics of diltiazem and one of its metabolites, desacetyldiltiazem in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after oral administration of diltiazem (15 mg/kg) in rats pretreated with morin (1.5, 7.5, and 15 mg/kg). Compared with the control group (given diltiazem alone), pretreatment of morin significantly increased the absorption rate constant (Ka) and peak concentration (Cmax) of diltiazem (p<0.05, p<0.01). Area under the plasma concentration-time curve (AUC) of diltiazem in rats pretreated with morin were significantly higher than that in the control group (p<0.05., p<0.01), hence the absolute bioavailability (AB%) of diltiazem was significantly higher than that of the control group (p<0.05, p<0.01). Relative bioavailability (RB%) of diltiazem in rats pretreated with morin was increased by 1.36-to 2.03-fold. The terminal half-life (t1/2) and time to reach the peak concentration (Tmax) of diltiazem were not altered significantly with morin pretreatment. AUC of desacetyldiltiazem was increased significantly (p<0.05) in rats pretreated with morin at doses of 7.5 and 15 mg/kg, but metabolite-parent ratio (MR) of desacetyldiltiazem was decreased significantly (p<0.05), implying that pretreatment of morin could be effective to inhibit the CYP 3A4-mediated metabolism of diltiazem. There were no apparent changes of Tmax and t1/2 of desacetyldiltiazem with morin pretreatment. Collectively, the pretreatment of morin significantly altered pharmacokinetics of diltiazem, which can be attributed to increased intestinal absorption as well as reduced first-pass metabolism. Based on these results, dose modification should be taken into consideration when diltiazem is used concomitantly with morin or morin-containing dietary supplements in clinical setting.

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Authors and Affiliations

  1. College of Pharmacy, Chonnam National University, Gwangju, Korea

    Hyun Jin Choi

  2. College of Pharmacy, Chosun University, 375 Seosuk-Dong, Dong-Gu, 501-759, Gwangju, Korea

    Jun-Shik Choi

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  1. Hyun Jin Choi
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Correspondence to Jun-Shik Choi.

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An erratum to this article is available at http://dx.doi.org/10.1007/BF02973918.

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Choi, H.J., Choi, JS. Effects of morin pretreatment on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem in rats. Arch Pharm Res 28, 970–976 (2005). https://doi.org/10.1007/BF02973885

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