흰쥐에서 플루바스타틴이 딜디아젬 및 그 대사체인 데스아세틸딜티아젬의 약물동태에 미치는 영향

• 영문명: Effect of Fluvastatin on the Pharmacokinetics of Diltiazem and its Metabolite, Desacetyldiltiazem in Rats
• 발행기관: 대한약학회
• 저자명: 박영길(Yong-Ji) 최준식(Jun-Shik Choi)
• 간행물 정보: 『약학회지』제50권 제2호 (2006년), 118~123쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2006.04.30

영문 초록

The aim of this study was to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were deter- mined after an oral administration of diltiazem (15㎎/㎏) to rats pretreated with fluvastatin (0.5 and 1.5 ㎎/㎏). Compared with the control (given diltiazem alone), the pretreatment of fluvastatin significantly (p<0.05) increased the area under the plasma concentration (AUC), peak plasma concentration (CMAX) and Ka of diltiazem. Relative bioavailability (RB%) of dil- tiazem increased from 1.36- to 1.55-fold. However there were no significant changes in tmax, kel and t1/2 of diltiazem. The pretreatment of fluvastatin also altered the pharmacokintic parameters of desacetyldiltiazem. The pretreatment of fluvastin (1.5 ㎎/㎏)significantly (p<0.05) increased the AUC of desacetyldiltiazem, whereas the metabolite parent ratio (MR) of desacetyldiatiazem was decreased significantly (p<0.05), suggesting that fluvastatin might inhibit the metabolism of diltiazem, The pretreatment of fluvastatin enhanced the bioavailability of diltiazem in a dose dependent manner at doses ranging from 0.5 to 1.5 ㎎/㎏, Further studies for the drug interaction will be needed in the clinical trials when dilitazem is administrated concomitantly with fluvastatin in humans.

키워드

diltiazem desacetyldiltiazem pharmacokinetics fluvastatin rats