Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol

被引:59
作者
Jones, AW [1 ]
Jönsson, KÅ
Kechagias, S
机构
[1] Linkoping Univ Hosp, Natl Lab Forens Chem, Dept Forens Toxicol, S-58185 Linkoping, Sweden
[2] Linkoping Univ Hosp, Dept Clin Pharmacol, S-58185 Linkoping, Sweden
[3] Linkoping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden
关键词
bioavailability; blood ethanol; first-pass metabolism; food; liver blood flow; macronutrients; pharmacokinetics;
D O I
10.1046/j.1365-2125.1997.t01-1-00620.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol. Methods Nine healthy men received ethanol (0.30 g kg(-1) body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating; a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min. Results The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6+/-4.0, 17.7+/-7.1, and 13.3+/-4.0 mg dl(-1) (mean+/-s.d.) after fat, CHO, and protein-rich meals and 30.8+/-4.3 and 54.3+/-6.4 mg dl(-1) after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUG) were 1767+/-549, 1619+/-760, 1270+/-406 mg dl(-1) min after fat, CHO, and protein-rich meals compared with 3210+/-527 and 4786+/-446 mg dl(-1) after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1-2 h in the fed-state. Conclusions Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as orle consequence of Michaelis-Menten elimination kinetics.
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页码:521 / 526
页数:6
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