Quantifying pharmacodynamic interaction between atenolol and valsartan

• Authors: Zuzana Rausova , Jana Chrenova , Viliam Mojto , Ladislav Dedik
• Languages of publication: EN

Abstracts

EN

We used mathematical modeling in order to determine the pharmacodynamic relationship between antihypertensive drugs atenolol and valsartan, by evaluating their effects on heart rate (HR), systolic blood pressure (SP) and diastolic blood pressure (DP). A group of twelve healthy male volunteers received a single oral dose of 100 mg of atenolol and 160 mg of valsartan, both separately and in combination. Pharmacokinetic (PK), pharmacokinetic/pharmacodynamic (PK/PD) and pharmacodynamic (PD) systems were proposed and PD model of atenolol and valsartan concentration-time profiles and PK/PD model of blood pressure and heart rate effects after administration of single doses of atenolol and valsartan and their combination were constructed. Parameters of PD system, such as gain and mean effect time, were obtained by analysis of PK and PK/PD systems. Modeling of PK and PK/PD systems and their analysis to obtain the PD results could considerably change the view o treatment of individual diseases in terms of greater knowledge of pharmacokinetics and pharmacodynamics of drugs.

Keywords

EN

Atenolol; Blood pressure; Mathematical modeling; Pharmacodynamics; Pharmacokinetics; Valsartan

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2014
• Volume: 9
• Issue: 1
• Pages: 1-9

Dates

published

1 - 2 - 2014

online

4 - 2 - 2014

Contributors

author

Zuzana Rausova

• Institute of Automation, Measurement and Applied Informatics, Faculty of Mechanical Engineering, Slovak University of Technology, 812 31, Bratislava, Slovakia

author

Jana Chrenova

• Institute of Automation, Measurement and Applied Informatics, Faculty of Mechanical Engineering, Slovak University of Technology, 812 31, Bratislava, Slovakia

author

Viliam Mojto

• IIIrd Department of Internal Medicine, Derer’s University Hospital, 833 05, Bratislava, Slovakia

author

Ladislav Dedik

• Institute of Automation, Measurement and Applied Informatics, Faculty of Mechanical Engineering, Slovak University of Technology, 812 31, Bratislava, Slovakia

References

• [1] Del Giaccio A., Eblen-Zajjur A., Cardiovascular drugs in human mechanical nociception: digoxin, amlodipine, propranolol, pindolol and atenolol, Invest Clin., 2010, 51, 77–86
• [2] Volpe M., Preventing cardiovascular events with angiotensin II receptor blockers: a closer look at telmisartan and valsartan, Expert Rev Cardiovasc Ther., 2012, 10, 1061–72, DOI: 10.1586/erc.12.80 http://dx.doi.org/10.1586/erc.12.80[Crossref]
• [3] Díez J., Review of the molecular pharmacology of Losartan and its possible relevance to stroke prevention in patients with hypertension, Clin Ther., 2006, 28, 832–48 http://dx.doi.org/10.1016/j.clinthera.2006.06.002[Crossref]
• [4] Antalóczy Z., Kékes E., Anti-anginal effect of Tenormin (atenolol), Ther Hung, 1992, 40, 58–63 [PubMed]
• [5] Bhatia V., Bhatia R., Mathew B., Angiotensin receptor blockers in congestive heart failure: evidence, concerns, and controversies, Cardiol Rev., 2005, 13, 297–303 http://dx.doi.org/10.1097/01.crd.0000148236.34855.18[Crossref]
• [6] Jugdutt B.I., Valsartan in the treatment of heart attack survivors, Vasc Health Risk Manag., 2006, 2, 125–38 http://dx.doi.org/10.2147/vhrm.2006.2.2.125[Crossref]
• [7] Carré A., (1998). Pharmacologic importance of the combination atenolol/nifedipine in hypertensive patients, Drugs, 1998, 56 Suppl 2, 23–30 http://dx.doi.org/10.2165/00003495-199856002-00003[Crossref]
• [8] Morgan J.M., Palmisano M., Piraino A., Hirschhorn W., Spencer S., Prasad P.P., Ortiz M., Lloyd P., The effect of valsartan on the angiotensin II pressor response in healthy normotensive male subjects. Clin Pharmacol Ther., 1997, 61, 35–44 http://dx.doi.org/10.1016/S0009-9236(97)90180-6[Crossref]
• [9] Hill A.V., The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves, J Physiol, 1910, 40, iv–vii
• [10] Mager D.E., Wyska E., Jusko W.J., Diversity of mechanism-based pharmacodynamic models. Drug Metab Dispos., 2003, 31, 510–8 http://dx.doi.org/10.1124/dmd.31.5.510[Crossref]
• [11] L. Dedík, M. Ďurišová, Advanced system approach based methods for modeling biomedical systems, in: International Conference of Computational Methods in Sciences and Engineering (ICCMSE 2004), eds. T. Simos and G. Maroulis, pp. 136–139 (Koninklijke Brill NV, Leiden, Netherlands, 2004)
• [12] M. Ďurišová, L. Dedík, New mathematical methods in pharmacokinetic modeling, Basic Clin. Pharmacol. Toxicol. 96 (2005) 335–342 http://dx.doi.org/10.1111/j.1742-7843.2005.pto_01.x[Crossref]
• [13] Czendlik CH., Sioufi A., Preiswerk G., Howald H., Pharmacokinetic and pharmacodynamic interaction of single doses of valsartan and atenolol. Eur J Clin Pharmacol, 1997, 52, 451–459 http://dx.doi.org/10.1007/s002280050318[Crossref]
• [14] Rosenbaum D.A., Is dynamical systems modeling just curve fitting?. Motor Control,1998, 2, 101–104 [PubMed]
• [15] Dedík L., Ďurišová M., System approach in technical, environmental, and bio-medical studies, 1999, Slovak University of Technology, Bratislava
• [16] Akaike H., Canonical correlation analysis of time series and the use of an information criterion. In: Mehra R.K., Lainiotis D.G. (Eds.), System Identification: Advances and Case Studies. (pp 27–96). Academic Press, New York, 1976 http://dx.doi.org/10.1016/S0076-5392(08)60869-3[Crossref]
• [17] Najib N.M., Idkaidek N., Adel A., Mohammed B., Al-Masri S., Admour I., Alam S.M., Dham R., Qumaruzaman., Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin and Tenormin) in healthy human volunteers. Biopharm Drug Dispos., 2005, 26, 1–5 http://dx.doi.org/10.1002/bdd.416[Crossref]
• [18] Spahn H., Kirch W., Mutschler E., Ohnhaus E.E., Kitteringham N.R., Lögering H.J., Paar D., Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol. Br J Clin Pharmacol., 1984, 17Suppl 1,97S–102S http://dx.doi.org/10.1111/j.1365-2125.1984.tb02439.x[Crossref]
• [19] Wu F.L., Chen P.F., Lee Y.J., Chen R.R.L., Comparative Pharmacokinetics of Two Atenolol Products. J Food Drug Anal, 2003, 11, 4–7
• [20] Spínola A.C., Almeida S., Filipe A., Neves R., Trabelsi F., Farré A., Results of a single-center, single-dose, randomized-sequence, open-label, two-way crossover bioequivalence study of two formulations of valsartan 160-mg tablets in healthy volunteers under fasting conditions. Clin Ther., 2009, 31, 1992–2001. DOI: 10.1016/j.clinthera.2009.09.002. http://dx.doi.org/10.1016/j.clinthera.2009.09.002[Crossref]
• [21] Zakeri-Milani P., Valizadeh H., Islambulchilar Z., Nemati M., Pharmacokinetic and bioequivalence study of two brands of valsartan tablets in healthy male volunteers. Arzneimittelforschung, 2010, 60,76-80. DOI: 10.1055/s-0031-1296252. [Crossref]
• [22] Sioufi A., Marfil F., Jaouen A., Cardot J.M., Godbillon J., Ezzet F., Lloyd P., The effect of age on the pharmacokinetics of valsartan. Biopharm Drug Dispos., 1998, 19, 237–44 http://dx.doi.org/10.1002/(SICI)1099-081X(199805)19:4<237::AID-BDD100>3.0.CO;2-7[Crossref]

Identifiers

DOI

10.2478/s11536-013-0252-8