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DOI: 10.1055/s-0033-1341424
Pharmacokinetics of Angiotensin II Receptor Blockers in the Dog Following a Single Oral Administration
Publikationsverlauf
received 22. Januar 2013
accepted 28. Februar 2013
Publikationsdatum:
28. März 2013 (online)
![](https://www.thieme-connect.de/media/drugres/201307/lookinside/thumbnails/10.1055-s-0033-1341424-1.jpg)
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.
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References
- 1 Dina R, Jafari M. Angiotensin II-receptor antagonists: an overview. Am J Health Syst Pharm 2000; 57: 1231-1241
- 2 Schiffrin EL. Vascular and cardiac benefits of angiotensin receptor blockers. Am J Med 2002; 113: 409-418
- 3 White WB, Lacourciere Y, Davidai G. Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period. Am J Hypertens 2004; 17: 347-353
- 4 Xi GL, Cheng JW, Lu GC. Meta-analysis of randomized controlled trials comparing telmisartan with losartan in the treatment of patients with hypertension. Am J Hypertens 2008; 21: 546-552
- 5 Sasaki T, Noda Y, Yasuoka Y et al. Comparison of the effects of telmisartan and olmesartan on home blood pressure, glucose, and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome. Hypertens Res 2008; 31: 921-929
- 6 Manova MM, Stoimenova A, Clerfeuille F et al. Impact of generic competition on market share and prices of cardiovascular medicines on the Bulgarian pharmaceutical market. J Public Health 2011; 19: 91-100
- 7 Israili ZH. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens 2000; 14: 73-86
- 8 Munger MA. Use of Angiotensin receptor blockers in cardiovascular protection: current evidence and future directions. PT 2011; 36: 22-40
- 9 Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001; 23: 1296-1310
- 10 Lentz KA. Current methods for predicting human food effect. AAPS J 2008; 10: 282-288
- 11 Akaike HA. New Look at the Statistical Model Identification. IEEE Trans Automat Contr 1974; 19: 716-723
- 12 D’Argenio DZ, Schumitzky A. ADAPT II User’s Guide: Pharmacokinetic/ Pharmacodynamic Systems Analysis Software. Biomedical Simulations Resource, Los Angeles. 1997
- 13 Kuentz M, Nick S, Parrott N et al. A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. Eur J Pharm Sci 2006; 27: 91-99
- 14 Patel B, Parikh RH, Swarnkar D. Enhancement of dissolution of Telmisartan through use of solid dispersion technique – surface solid dispersion. J Pharm Bioallied Sci 2012; 4: 64-68
- 15 Volpe M, Tocci G. Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic. Vasc Health Risk Manag 2012; 8: 371-380
- 16 Rizos CV, Milionis HJ, Kostapanos MS et al. Effects of rosuvastatin combined with olmesartan, irbesartan, or telmisartan on indices of glucose metabolism in Greek adults with impaired fasting glucose, hypertension, and mixed hyperlipidemia: a 24-week, randomized, open-label, prospective study. Clin Ther 2010; 32: 492-505
- 17 Sutton SC. Companion animal physiology and dosage form performance. Adv Drug Deliv Rev 2004; 56: 1383-1398
- 18 Mitra A, Wu Y. Challenges and opportunities in achieving bioequivalence for fixed-dose combination products. AAPS J 2012; 14: 646-655