title: Effects of itraconazole, dexamethasone and naringin on the pharmacokinetics of nadolol in rats.
abstract: 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 β-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 (AUC₀₋∞)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 AUC₀₋∞ 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.
authors: Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
authors: Nozomu
authors: N
authors: Miyazaki
authors: Shingen
authors: S
authors: Misaka
authors: Hiroshi
authors: H
authors: Ogata
authors: Tetsuhito
authors: T
authors: Fukushima
authors: Junko
authors: J
authors: Kimura
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D017272:Celiprolol / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D017964:Itraconazole / Q000494:pharmacology*; D008297:Male; D009248:Nadolol / Q000493:pharmacokinetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000319:Adrenergic beta-Antagonists; D044950:Flavanones; D029362:Organic Anion Transporters, Sodium-Independent; C421102:Slco1a1 protein, rat; C421143:Slco1a5 protein, rat; D017964:Itraconazole; D009248:Nadolol; D003907:Dexamethasone; D017272:Celiprolol; C005274:naringin