Pharmacokinetic interaction between alcohol and two of the commonly prescribed anti-hypertensive drugs-amlodipine and nebivolol

Geethalakshmi Gunasekaran, Ruckmani A., Arjun Arumugam Olaganathan, Arun Kumar R.


Background: Alcoholism is one of the leading causes of secondary hypertension. Many a times in clinical setting, many hypertensive patients also happen to be alcoholics, either social/moderate drinkers or suffer from alcohol dependence. For these patients, cessation of alcohol consumption is advocated and counselled as part of diet and lifestyle modifications. However, compliance rates have been found to be variable. Therefore, these patients consume alcohol and also take anti-hypertensive medications on a day-to-day basis. This study was initiated to explore influence of alcohol on the pharmacokinetics of anti-hypertensive drugs – Amlodipine and Nebivolol.

Methods: 24 human volunteers were recruited for the study after obtaining informed consent. 12 volunteers each for Amlodipine, Nebivolol and alcohol’s effect on the drugs respectively were evaluated. Two standard drinks of alcohol were administered in respective period as per randomization. Clinical confinement and blood sampling was carried out as per ethics committee approved protocol in accordance with good clinical practice principles.

Plasma samples were analyzed using validated LC-MS/MS bio-analytical method, for quantification of Nebivolol and Amlodipine in lines with good laboratory practice principles. Pharmacokinetic and statistical analysis of results was evaluated using WinNonlin Version 5.3.

Results: The pharmacokinetic parameters were evaluated statistically and ANOVA results suggest that despite changes in individual parameters, the bioavailability was comparable, as both Cmax and AUC0-inf were well within the range of 80-125%.

Conclusions: It is clearly observed that there are variations in all pharmacokinetic parameters when the drug is administered with alcohol. However, the same are well within acceptable limits and bioavailability of the drugs is comparable when administered with alcohol. Hence, two standard drinks of alcohol have limited effect on the pharmacokinetics of Amlodipine and Nebivolol. Further studies are required to evaluate influence of higher and frequent doses of alcohol on pharmacokinetics of Amlodipine and Nebivolol.


Alcohol, Anti-hypertensives, Bioavailbility, Pharmacokinetics

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World Health Organization. A global status report on alcohol and health; Geneva, World Health Organization; 2014.

Country profile by World Health Organization. Global status report on alcohol and health. XIII; 2014.

World Health Organization. A global brief on Hypertension; Geneva, World Health Organization; 2013.

World Health Organization. Causes of death: Data sources and methods. 2008. Available at Accessed Oct 2015.

Lim S, Vos T, Flaxman A, Danaei G, Shibuya K, Adair-Rohani H. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;380(9859):2224-60.

Gupta R, Guptha S. Strategies for initial management of hypertension. Indian Journal of Medical Research. 2010;132(5):531-42.

Gupta R, al-Odat NA, Gupta VP. Hypertension epidemiology in India: meta- analysis of 50 years prevalence rates and blood pressure trends. Journal of Human Hypertension. 1996;10(7):465-72.

Mohan V. e-Prevalence, awareness and control of hypertension in Chennai. The Chennai Urban Rural Epidemiology Study (CURES-52); 2015.

Madhukumar S, Gaikwad V. An Epidemiological Study of Hypertension and its risk factors in rural Population of Bangalore Rural District. AJMS. 2012;5(3):264-70.

Guidance for Industry Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs-General Considerations; 2014.

U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug. Evaluation and Research (CDER). 2001.

Zaman R, Wilkins M, Kendall M, Jack D. The effect of food and alcohol on the pharmacokinetics of acebutolol and its metabolite, diacetolol. Biopharm Drug Dispos. 1984;5(1):91-5.

MHRA. Public assessment report Nebivolol 5 mg tablets. Available at Accessed Oct 2015.

EMA Public assessment report. Nebivolol Scientific discussion. Available at Accessed Oct

USFDA Approved drug products. Amlodipine besylate. Available at Accessed Oct 2015

Kumar S, Earla R, Jin M, Mitra A, Kumar A. Effect of ethanol on spectral binding, inhibition, and activity of CYP3A4 with an antiretroviral drug nelfinavir. Biochemical and Biophysical Research Communications. 2010;402(1):163-67.

Zhu Y, Wang F, Li Q, Zhu M, Du A, Tang W. Amlodipine Metabolism in Human Liver Microsomes and Roles of CYP3A4/5 in the Dihydropyridine Dehydrogenation. Drug Metabolism and Disposition. 2013;42(2):245-9.

Vincent-Viry M. The Effects of Drinking and Smoking on the CYP2D6 Metabolic Capacity. ASPET. 2000;28(6).