title: Pharmacokinetics of angiotensin II receptor blockers in the dog following a single oral administration.
abstract: Angiotensin II receptor blockers (ARBs) are effective and well-tolerated orally active anti-hypertensive agents. The purpose of this study was to investigate the pharmacokinetic properties of typical ARBs in the dog. 60 beagles were administered a single oral dose of Micardis® 80 mg (telmisartan), Cozaar® 50 mg (losartan), or Diovan® 80- and 160-mg (valsartan). The plasma concentrations of these ARBs were measured using liquid chromatography/tandem mass spectrometry and their pharmacokinetic properties were analyzed using both non-compartmental and compartmental approaches. The half-life and volume of distribution in dogs were in the order losartan>valsartan>telmisartan after oral administration. Systemic exposure was estimated by calculating the area under the plasma concentration-vs.-time curve from time zero to infinity (AUC inf ), and resulted in the order telmisartan>valsartan>losartan. The values of C max and AUC increased in proportion to the dose of valsartan. In compartmental analysis, the pharmacokinetics of telmisartan and losartan pharmacokinetics fit a 2-compartment model, while valsartan fit a 1-compartment model. These results provide detailed pharmacokinetic information of ARBs in the dog, and may aid in future development of improved formulations or fixed-dose combinations.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, South Korea.
authors.forename: I-H
authors.initials: IH
authors.lastname: Baek
authors.forename: B-Y
authors.initials: BY
authors.lastname: Lee
authors.forename: E-S
authors.initials: ES
authors.lastname: Lee
authors.forename: K-I
authors.initials: KI
authors.lastname: Kwon
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001565:Benzoates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D019808:Losartan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D053719:Tandem Mass Spectrometry / Q000379:methods; D000077333:Telmisartan; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D019808:Losartan; D000077333:Telmisartan