2013年8月
Effects of Itraconazole, Dexamethasone and Naringin on the Pharmacokinetics of Nadolol in Rats
DRUG METABOLISM AND PHARMACOKINETICS
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- 巻
- 28
- 号
- 4
- 開始ページ
- 356
- 終了ページ
- 361
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.2133/dmpk.DMPK-12-RG-111
- 出版者・発行元
- JAPANESE SOC STUDY XENOBIOTICS
The aim of the present study was to clarify the involvement of P-glycoprotein (P-gp) or organic anion transporting polypeptide (Oatp) 1a5 in the pharmacokinetics of nadolol (NDL), a non-metabolized hydrophilic beta-adrenoceptor blocker, in rats. Pretreatment with itraconazole (ICZ, P-gp inhibitor, 50 mg/kg) for 30 min before oral administration of NDL (10 mg/kg) significantly increased the area under the plasma concentration-time curve (AUC(0-infinity)) of NDL by 1.7-fold compared with control. Intragastric administration of dexamethasone (DEX, 8 mg/kg) for 4 consecutive days increased P-gp level in the intestine and the liver. In line with this, DEX pre-treatment decreased maximum plasma concentration (C-max) of NDL by 28% of control. To inhibit the intestinal Oatp1a5, naringin (NRG, 0.145 mg/kg) was preadministered orally for 30 min before the oral administrations of NDL or celiprolol (CEL, 10 mg/kg, Oatp1a5 substrate). Although NRG markedly reduced C-max and AUC(0-infinity) of CEL by 60% and 65% of control, respectively, little difference was observed in the plasma concentration of NDL between NRG and control. These results suggest that P-gp is greatly involved in the pharmacokinetics of NDL, while the involvement of Oatp1a5 in the pharmacokinetics of NDL may be less than that of celiprolol in rats.
- リンク情報
- ID情報
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- DOI : 10.2133/dmpk.DMPK-12-RG-111
- ISSN : 1347-4367
- Web of Science ID : WOS:000322928100010