Is debrisoquine hydroxylation modified during acute viral hepatitis?
Drug metabolism in the liver may be decreased during liver diseases. However, the extent of impairment of specific isozymes of cytochrome P450 is largely unknown. We have studied the debrisoquine hydroxylation capacity of 17 patients with acute viral hepatitis and 106 unrelated healthy subjects. Debrisoquine metabolic ratio was increased in extensive metabolizers (EM) with acute viral hepatitis as compared with healthy EMs (median metabolic ratio: 1.20 vs 0.84, P < 0.05). However, there was no difference in phenotype prevalence between patients and controls. Our results suggest that acute viral hepatitis only has a marginal effect on the activity of CYP2D6 and that substrates of this enzyme may be given in normal therapeutic doses to this category of patients.
Joanne
C
C
Department of Clinical Pharmacology, CHU Jean Minjoz, Besançon, France.
Paintaud
G
G
Bresson-Hadni
S
S
Magnette
J
J
Becker
M C
MC
Miguet
J P
JP
Bechtel
P R
PR
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016001:Confidence Intervals; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006525:Hepatitis, Viral, Human / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010641:Phenotype
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin