RELATIONSHIP BETWEEN CYTOCHROME-P-450 INDUCTION BY RIFAMPICIN, HEPATIC VOLUME AND PORTAL BLOOD-FLOW IN MAN

Objective: Induction of hepatic cytochrome P-450-dependent oxidative m etabolism is related to an almost identical increase (30%) in both the liver weight and portal blood flow in animals. In humans by contrast, an increased liver blood flow (44%) but no significant increase in li ver volume has been reported. Design: Therefore, we studied prospectiv ely the relationship between P-450 induction by rifampicin, hepatic vo lume and portal blood flow in 10 healthy volunteers. Methods: After a pre-treatment phase (day 1 to 7) the 10 volunteers received 600 mg/day of rifampicin from day 7 to 12. The urinary 6-beta-hydroxycortisol ou tput as a measure of oxidative metabolism (CYP3A4) and portal blood fl ow (pulsed Doppler ultrasound) were determined on days 1, 7, 11 and 13 . Hepatic magnetic resonance volumetry was performed on days 1 and 13. Results: Urinary 6-beta-hydroxycortisol output increased in all volun teers (P = 0.0051) from a median of 2.15 mu g/day/kg (1.8-3.3 mu g/day /kg) on day 1 to 9.9 mu g/day/kg (5.7-14 mu g/day/kg) on day 13. In 9 of 10 volunteers induction by rifampicin was related to an increase (P = 0.0218) in liver volume from a median of 1570 c(3) (1390-1830 cm(3) ) to a median of 1690 cm(3) (1420-1860 cm(3)). The portal flow as asse ssed by colour Doppler ultrasound did not change significantly between day 1 (median 22cm/s (15-35cm/s)) and day 13 (median 19 cm/s (16-39cm /s)). Conclusion: A fourfold increase of urinary 6-beta-hydroxycortiso l output after induction of cytochrome P-450 by rifampicin is associat ed with a significant but less than 10% increase in human liver volume . No increase of portal perfusion as assessed by Doppler ultrasound co uld be detected in this study.