Growth hormone treatment increases cytochrome p450-mediated antipyrine clearance in man

被引:44
作者
Cheung, NW
Liddle, C
Coverdale, S
Lou, JC
Boyages, SC
机构
[1] UNIV SYDNEY, WESTMEAD HOSP, DEPT CLIN PHARMACOL, WESTMEAD, NSW 2145, AUSTRALIA
[2] UNIV SYDNEY, WESTMEAD HOSP, DEPT GASTROENTEROL & HEPATOL, WESTMEAD, NSW 2145, AUSTRALIA
[3] UNIV SYDNEY, WESTMEAD HOSP, STORR LIVER UNIT, WESTMEAD, NSW 2145, AUSTRALIA
关键词
D O I
10.1210/jc.81.5.1999
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We used the antipyrine clearance test (APC) to examine the effect of growth hormone (GH) therapy on hepatic cytochrome P450 (CYP) enzyme activity. Eleven GH deficient adults were randomized to receive GH or placebo for 6 months, all subjects subsequently received GH. Before treatment, APC was below the normal range in six subjects. we found an increase in APC in the subjects randomized to receive GH compared to those on placebo (median change +0.14 ml/min/kg [range +0.04 to +0.20] vs -0.04 ml/min/kg [range -0.07 to +0.04], p = 0.011). The stimulatory effect of GH on drug metabolism was confirmed by the data for 3 months GH treatment in all 11 subjects, with APC increasing from 0.33 ml/min/kg (range 0.22 to 0.69) to 0.50 ml/min/kg (range 0.27 to 0.83), p = 0.018). These data indicate that GH modulates hepatic CYP activity. This has important clinical implications, as the hepatic metabolism of drugs and hormones may be altered in patients undergoing GH therapy.
引用
收藏
页码:1999 / 2001
页数:3
相关论文
共 13 条
[1]  
CHEUNG NW, IN PRESS J CLIN ENDO
[2]   ACCURACY AND CLINICAL UTILITY OF SIMPLIFIED TESTS OF ANTIPYRINE METABOLISM [J].
FARRELL, GC ;
ZALUZNY, L .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1984, 18 (04) :559-565
[3]   DRUG-METABOLISM IN EXTRAHEPATIC DISEASES [J].
FARRELL, GC .
PHARMACOLOGY & THERAPEUTICS, 1987, 35 (03) :375-404
[4]   EFFECTS OF GROWTH-HORMONE THERAPY ON THYROID-FUNCTION OF GROWTH HORMONE-DEFICIENT ADULTS WITH AND WITHOUT CONCOMITANT THYROXINE-SUBSTITUTED CENTRAL HYPOTHYROIDISM [J].
JORGENSEN, JOL ;
PEDERSEN, SA ;
LAURBERG, P ;
WEEKE, J ;
SKAKKEBAEK, NE ;
CHRISTIANSEN, JS .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1989, 69 (06) :1127-1132
[5]   CYCLOSPORINE METABOLISM IN HUMAN-LIVER - IDENTIFICATION OF A CYTOCHROME-P-450III GENE FAMILY AS THE MAJOR CYCLOSPORINE-METABOLIZING ENZYME EXPLAINS INTERACTIONS OF CYCLOSPORINE WITH OTHER DRUGS [J].
KRONBACH, T ;
FISCHER, V ;
MEYER, UA .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1988, 43 (06) :630-635
[6]  
LEVITSKY LL, 1989, DEV PHARMACOL THERAP, V12, P90
[7]   CONSTITUTIVE EXPRESSION AND HORMONAL-REGULATION OF MALE SEXUALLY DIFFERENTIATED CYTOCHROMES-P450 IN PRIMARY CULTURED RAT HEPATOCYTES [J].
LIDDLE, C ;
MODE, A ;
LEGRAVEREND, C ;
GUSTAFSSON, JA .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1992, 298 (01) :159-166
[8]  
LIDDLE C, 1994, HEPATOLOGY, V20, pA185
[9]  
MORGAN ET, 1985, J BIOL CHEM, V260, P1895
[10]  
REDMOND GP, 1980, PEDIATR PHARMACOL, V1, P63