Publication:

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

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.