Transport characteristics of candesartan in human intestinal Caco-2 cell line.
The intestinal absorptive characteristics and the efflux mechanisms of candesartan (CDS), a novel angiotensin II type 1 receptor blocker, were investigated. The Caco-2 cells were used as models of the intestinal mucosa to assess uptake and transport of CDS. The determination of CDS was performed by HPLC-Flu. In the Caco-2 cells, the uptake and absorptive transport of CDS were pH-independent (in the pH range 6.0-8.0). Passive membrane diffusion dominates the absorptive transport behavior of CDS across Caco-2 cells, while secretory transport was a concentration-dependent and saturable process. In the presence of cyclosporin A and verapamil, potent inhibitors of P-glycoprotein (P-gp), the P(ratio) decreased from 3.8 to 2.3 and 1.8, respectively, and permeation of apical to basolateral was enhanced. Overall, the current study suggests that efflux transporters are capable of mediating the absorption and secretion of CDS, and they may play significant roles in limiting the oral absorption of CDS.
Zhou
Lingjie
L
Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai 200032, P R China.
Chen
Xiaoping
X
Gu
Yuanqing
Y
Liang
Jianying
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D001713:Biphenyl Compounds; D018938:Caco-2 Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000494:pharmacology; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D013777:Tetrazoles; D016572:Cyclosporine; D014700:Verapamil; C081643:candesartan