INCREASED METABOLISM OF ACETAMINOPHEN IN CHRONICALLY ALCOHOLIC PATIENTS

被引:18
作者
GIRRE, C
HISPARD, E
PALOMBO, S
NGUYEN, C
DALLY, S
机构
[1] Clinique Toxicologique Hopital F. Widal, Paris
关键词
ACETAMINOPHEN; ALCOHOLISM; HEPATOTOXICITY; PHARMACOKINETICS; BIOAVAILABILITY;
D O I
10.1111/j.1530-0277.1993.tb00743.x
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
The aim of this work was to determine whether the metabolism of acetaminophen increases in chronic alcoholics, and consequently whether the production of its hepatotoxic metabolite is enhanced. For this purpose, the pharmacokinetics of acetaminophen were compared in 12 alcoholic men and 12 healthy controls. After a 12-hr fast, the patients (on the 3rd hospital day) and volunteers were given 1 g of oral acetaminophen at 8.00 AM. Venous blood samples were drawn before drug intake and at regular intervals after to evaluate plasma acetaminophen concentrations. The elimination half-life of acetaminophen was significantly shorter in the alcoholic patients than in the controls (1.70 +/- 0.55 vs. 2.84 +/- 0.30 hr, p < 0.001). Similarly, total plasma acetaminophen clearance was significantly higher in the patients than in the controls (29.19 +/- 13.37 vs. 24.45 +/-11.10 1/hr, p < 0.05). These results confirm that the metabolism of acetaminophen increases in chronic alcoholism and consequently suggest that its potential liver toxicity might be enhanced.
引用
收藏
页码:170 / 173
页数:4
相关论文
共 17 条
[1]  
AEDRIENSSEN PI, 1978, BR J CLIN PHARM, V6, P87
[2]   INTERACTION OF ETHANOL WITH ACETAMINOPHEN METABOLISM IN THE BABOON [J].
ALTOMARE, E ;
LEO, MA ;
SATO, C ;
VENDEMIALE, G ;
LIEBER, CS .
BIOCHEMICAL PHARMACOLOGY, 1984, 33 (14) :2207-2212
[3]   ACETAMINOPHEN, ALCOHOL, AND CYTOCHROME-P-450 [J].
BLACK, M ;
RAUCY, J .
ANNALS OF INTERNAL MEDICINE, 1986, 104 (03) :427-429
[4]  
CLARK R, 1973, LANCET, V1, P66
[5]  
CRITCHLEY JAJ, 1981, BR J CLIN PHARM, V13, pP276
[6]   CLINICAL PHARMACOKINETICS OF PARACETAMOL [J].
FORREST, JAH ;
CLEMENTS, JA ;
PRESCOTT, LF .
CLINICAL PHARMACOKINETICS, 1982, 7 (02) :93-107
[7]   EFFECT OF ABSTINENCE FROM ALCOHOL ON THE DEPRESSION OF GLUTATHIONE-PEROXIDASE ACTIVITY AND SELENIUM AND VITAMIN-E LEVELS IN CHRONIC-ALCOHOLIC PATIENTS [J].
GIRRE, C ;
HISPARD, E ;
THEROND, P ;
GUEDJ, S ;
BOURDON, R ;
DALLY, S .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1990, 14 (06) :909-912
[8]   CYTOCHROME-P-450 ENZYMES INVOLVED IN GENETIC-POLYMORPHISM OF DRUG OXIDATION IN HUMANS [J].
GUENGERICH, FP ;
BEAUNE, PH ;
UMBENHAUER, DR ;
CHURCHILL, PF ;
BORK, RW ;
DANNAN, GA ;
KNODELL, RG ;
LLOYD, RS ;
MARTIN, MV .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1987, 15 (04) :576-578
[9]   GLUTATHIONE DEFICIENCY IN ALCOHOLICS - RISK FACTOR FOR PARACETAMOL HEPATOTOXICITY [J].
LAUTERBURG, BH ;
VELEZ, ME .
GUT, 1988, 29 (09) :1153-1157
[10]   INTERACTION OF ETHANOL WITH DRUGS, HEPATOTOXIC AGENTS, CARCINOGENS AND VITAMINS [J].
LIEBER, CS .
ALCOHOL AND ALCOHOLISM, 1990, 25 (2-3) :157-176