HEPATITIS-A IMPAIRS THE FUNCTION OF HUMAN HEPATIC CYP2A6 IN-VIVO

Hepatitis virus A (HVA) is a worldwide sporadic disease but its effect s on pharmacokinetics and individual drug responses have not been stud ied. In this study, the 7-hydroxycoumarin (7OHC) excretion test used i n vivo as a bioindex of hepatic CYP2A6 activity was performed in 20, p reviously healthy, acute jaundice HVA patients. Volunteers with an acu te HVA were treated with one p.o. administration of 5 mg coumarin (Ven alot(R)). Among the patients, 11 were children (6-10 years; two girls and nine boys), the rest (15-40 years old) consisted of two men and se ven women. Urinary excretion of 7OHC was measured after overnight fast ing in four fractions: 0 h before any medication (to detect if any bas al 7OHC excretion exits), and after a 5-mg coumarin capsule p.o., 0-2, 2-4 and 4-8 h fractions were collected and urine volumes were recorde d. Urinary excretion of 7-hydroxycoumarin occurred to a similar extent in healthy adults and children. The first 2-h 7OHC excretion was decr eased by 26% (P < 0.05) and total (0-8 h) 7OHC excretion was decreased by 37% (P < 0.01) among HVA-positive adults (age range 15-40 years) c ompared with the values obtained from healthy volunteers. In 11 HVA-po sitive children (age 6-10 years), the first 2-h 7OHC excretion was onl y 20% (P < 0.0001) and the total 7OHC excretion 28% (P < 0.0001) of th e value observed in healthy controls. These results suggest that (i) a n acute HVA decreases the metabolic clearance of drugs such as coumari n which are rapidly metabolised by CYP2A6 and (ii) this decrease is ev en more prominent in children. Such metabolic responses may be of clin ical importance and may also interfere with other drug therapy in thes e patients. (C) 1997 Elsevier Science Ireland Ltd.