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Pharmaceutical Nanotechnology

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ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Simultaneous Determination of Telmisartan and Pitavastatin Calcium in Intestinal Perfusate by HPLC: Application to Intestinal Absorption Interaction Study

Author(s): Junying Wang, Juan Liu, Xiangrong Song and Chunmei Fu*

Volume 8, Issue 4, 2020

Page: [313 - 322] Pages: 10

DOI: 10.2174/2211738508666200607181727

Price: $65

Abstract

Background: Hypertension and hypercholesterolemia are two main physiological risk factors of cardiovascular disease, and commonly occur in combination. Multicompound combination therapy is rational for the treatment of concurrent hypertension and hypercholesterolemia, while telmisartan and pitavastatin calcium can be used as a potential drug combination.

Objective: The aim of this paper is to study the intestinal absorption and absorption interaction of telmisartan and pitavastatin calcium.

Methods: An HPLC method was developed and validated to determine telmisartan and pitavastatin calcium in intestinal perfusate simultaneously. The in situ single-pass perfusion in rats was utilized to investigate the effects of concentrations, intestinal segment (duodenum, jejunum, ileum and colon) and co-administrated drugs on absorption.

Results: The effective permeability coefficient and the absorption rate constant of telmisartan were higher in the duodenum as compared to other intestinal segments. However, the intestinal absorption of pitavastatin calcium was not segmental dependent. The effective permeability coefficient and absorption rate constant have no significant difference among three concentrations of telmisartan, pitavastatin calcium individually and their combination.

Conclusion: The results showed that telmisartan and pitavastatin calcium were transported passively, and telmisartan and pitavastatin calcium could be absorbed well in all intestinal segments. The intestinal absorption parameters revealed the absence of any intestinal absorption interaction when co-administered.

Lay Summary: Co-administration of telmisartan and pitavastatin calcium can provide a potential therapeutic strategy for the treatment of concurrent hypertension and hypercholesterolemia. We are investigating the intestinal interaction of these two drugs in rats using the developed HPLC method and in situ single-pass perfusion technology. We will calculate some parameters after administrating two types of drugs either separately or together, which help reflect changes regarding intestinal absorption and penetration. Compared with telmisartan and pitavastatin calcium administrated separately, if parameters significantly change after co-administration, it proves the existence of the intestinal interactions. Moreover, the results might contribute to clinic drug monitoring.

Keywords: Cardiovascular disease, HPLC, in situ single-pass perfusion, intestinal absorption interaction, pitavastatin, telmisartan.

Graphical Abstract
[1]
Roth GA, Nguyen G, Forouzanfar MH, Mokdad AH, Naghavi M, Murray CJ. Estimates of global and regional premature cardiovascular mortality in 2025. Circulation 2015; 132(13): 1270-82.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016021] [PMID: 26408271]
[2]
Rodriguez-Porcel M, Krier JD, Lerman A, et al. Combination of hypercholesterolemia and hypertension augments renal function abnormalities. Hypertension 2001; 37(2 Pt 2): 774-80.
[http://dx.doi.org/10.1161/01.HYP.37.2.774] [PMID: 11230372]
[3]
Jang JY, Lee SH, Kim BS, et al. Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients. Korean Circ J 2015; 45(3): 225-33.
[http://dx.doi.org/10.4070/kcj.2015.45.3.225] [PMID: 26023311]
[4]
Bertrand ME, Vlachopoulos C, Mourad JJ. Triple Combination therapy for global cardiovascular risk: atorvastatin, perindopril, and amlodipine. Am J Cardiovasc Drugs 2016; 16(4): 241-53.
[http://dx.doi.org/10.1007/s40256-016-0175-2] [PMID: 27256435]
[5]
Jackson R, Lawes CMM, Bennett DA, Milne RJ, Rodgers A. Treatment with drugs to lower blood pressure and blood cholesterol based on an individual’s absolute cardiovascular risk. Lancet 2005; 365(9457): 434-41.
[http://dx.doi.org/10.1016/S0140-6736(05)17833-7] [PMID: 15680460]
[6]
de Cates AN, Farr MRB, Wright N, et al. Fixed-dose combination therapy for the prevention of cardiovascular disease. Cochrane Db Syst Rev 2012; 4(4) CD009868
[http://dx.doi.org/10.1002/14651858.CD009868]
[7]
Molinengo L. [The pill: lights and shadows]. Minerva Nipiol 1968; 18(5): 136-9.
[PMID: 5745021]
[8]
Wiley B, Fuster V. The concept of the polypill in the prevention of cardiovascular disease. Ann Glob Health 2014; 80(1): 24-34.
[http://dx.doi.org/10.1016/j.aogh.2013.12.008] [PMID: 24751562]
[9]
Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326(7404): 1419.
[http://dx.doi.org/10.1136/bmj.326.7404.1419] [PMID: 12829553]
[10]
Yusuf S, Pais P, Sigamani A, et al. Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators. Circ Cardiovasc Qual Outcomes 2012; 5(4): 463-71.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.111.963637] [PMID: 22787067]
[11]
Patel A, Cass A, Peiris D, et al. A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk. Eur J Prev Cardiol 2015; 22(7): 920-30.
[http://dx.doi.org/10.1177/2047487314530382] [PMID: 24676715]
[12]
Galzerano D, Capogrosso C, Di Michele S, et al. New standards in hypertension and cardiovascular risk management: focus on telmisartan. Vasc Health Risk Manag 2010; 6(1): 113-33.
[http://dx.doi.org/10.2147/VHRM.S7857] [PMID: 20448797]
[13]
da Silva PM. Are all statins the same? Focus on the efficacy and tolerability of pitavastatin. Am J Cardiovasc Drugs 2011; 11(2): 93-107.
[http://dx.doi.org/10.2165/11591190-000000000-00000] [PMID: 21446776]
[14]
Betteridge J. Pitavastatin - results from phase III & IV. Atheroscler Suppl 2010; 11(3): 8-14.
[http://dx.doi.org/10.1016/S1567-5688(10)71064-3] [PMID: 21193153]
[15]
Xu C, Fang D, Chen X, et al. Effect of telmisartan on the therapeutic efficacy of pitavastatin in high-fat diet induced dyslipidemic guinea pigs. Eur J Pharmacol 2015; 762: 364-71.
[http://dx.doi.org/10.1016/j.ejphar.2015.06.005] [PMID: 26057693]
[16]
Schurgers N, Bijdendijk J, Tukker JJ, Crommelin DJ. Comparison of four experimental techniques for studying drug absorption kinetics in the anesthetized rat in situ. J Pharm Sci 1986; 75(2): 117-9.
[http://dx.doi.org/10.1002/jps.2600750203] [PMID: 3958918]
[17]
Fagerholm U, Johansson M, Lennernäs H. Comparison between permeability coefficients in rat and human jejunum. Pharm Res 1996; 13(9): 1336-42.
[http://dx.doi.org/10.1023/A:1016065715308] [PMID: 8893271]
[18]
Shen J, Wang-Chun DU, Song ZJ. In situ intestinal absorption of telmisartan and the effect of coadministrated drugs on its absorption in rats. Zhongguo Yiyuan Yaoxue Zazhi 2012; 32(22): 1805-8.
[19]
Burnier M. Telmisartan: a different angiotensin II receptor blocker protecting a different population? J Int Med Res 2009; 37(6): 1662-79.
[http://dx.doi.org/10.1177/147323000903700602] [PMID: 20146864]
[20]
Shen J, Jiao Z, Li Z, et al. Transport characteristics of telmisartan in human intestinal cell line Caco-2. Zhongguo Yaoxue Zazhi 2006; 41(21): 1624-7.
[21]
Dahan A, Amidon GL. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs. Mol Pharm 2009; 6(1): 19-28.
[http://dx.doi.org/10.1021/mp800088f] [PMID: 19248230]
[22]
Tam D, Tirona RG, Pang KS. Segmental intestinal transporters and metabolic enzymes on intestinal drug absorption. Drug Metab Dispos 2003; 31(4): 373-83.
[http://dx.doi.org/10.1124/dmd.31.4.373] [PMID: 12642462]
[23]
Jeong EJ, Liu Y, Lin H, Hu M. In situ single-pass perfused rat intestinal model for absorption and metabolism. Optim in Drug Disc 2004; pp. 65-76.
[http://dx.doi.org/10.1385/1-59259-800-5:065]
[24]
Dahan A, West BT, Amidon GL. Segmental-dependent membrane permeability along the intestine following oral drug administration: evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat. Eur J Pharm Sci 2009; 36(2-3): 320-9.
[http://dx.doi.org/10.1016/j.ejps.2008.10.013] [PMID: 19028572]
[25]
Zeng XY, Dong S, He NN, Jiang CJ, Dai Y, Xia YF. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration. Fitoterapia 2015; 105: 119-26.
[http://dx.doi.org/10.1016/j.fitote.2015.06.014] [PMID: 26102179]

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