The Influence of Alcohol on the Pharmacokinetics of Antipyrine.

Abstract

Alcohol-Drug/ Food interaction is a common pharmacokinetic interaction that can cause inter-individual variability in drug kinetics and response by influencing hepatic drug metabolism and related factors. This study was aimed at establishing the influence of alcohol on the pharmacokinetics of antipyrine which has often been used as an index of hepatic metabolizing capacity of the individual tested. Age and sex matched healthy volunteers were chosen respectively as control population (n =12, age = 18-32 years, weight=46-76 kg, males, non alcohol consuming) and study population (n=11, age=18-32 years, males, weight =50-80 kg, alcohol consumption =10-20 g of ethanol per week). Subjects were made to fast for 8 hours before the study. Each was then given 2 tablets of 270mg antipyrine trinitrate to swallow with 200ml of water on an empty stomach. 2 hours later, they were allowed to eat food and drink water. Alcohol ingestion and cigarette smoking were not allowed. Blood samples were then collected from each subject at times 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 15.0 hours. Plasma antipyrine was extracted by adding methanol, benzoic acid and distilled water to the plasma. The mixture was then centrifuged and filtered. The filtrate was injected into a high pressure liquid chromatography using reversed phase Bondesil C18 (0.5um) column, with benzoic acid (as internal standard) and acetonitrile: acetic acid (in 1% water) (35:65) as mobile phase. The concentrations of the antipyrine were determined from the chromatographic calibration output. The pharmacokinetic parameters of antipyrine in these subjects were compared with control using the Student's “t” test with significance in
the values of the elimination rate constant, elimination half-life, systemic (plasma) clearance, lag time, time to attain peak drug concentration and the area under the drug concentration-time curve (zero to 15 hours and zero to infinity respectively). However, parameters such as absorption half-life, absorption rate constant, the extrapolated plasma drug concentration at zero time, the peak plasma drug concentration and volume of distribution were not significantly different in the two populations (P >0.05). The precision of the method used in the study was checked by manual Peak height (PH) method of quantitation with precision of 1.1- 5.5 %. This study has shown that chronic alcohol ingestion increased the systemic clearance of antipyrine by decreasing its elimination half-life without affecting its absorption from the intestine and its distribution in the body.

Key words: Alcohol, drug-food interaction , antipyrine, pharmacokinetics