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 metabolism 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 liver volume has been reported.


METHODS
Therefore, we studied prospectively the relationship between P-450 induction by rifampicin, hepatic volume 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 output as a measure of oxidative metabolism (CYP3A4) and portal blood flow (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 volunteers (P = 0.0051) from a median of 2.15 micrograms/day/kg (1.8-3.3 micrograms/day/kg) on day 1 to 9.9 micrograms/day/kg (5.7-14 micrograms/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 cm3 (1390-1830 cm3) to a median of 1690 cm3 (1420-1860 cm3). The portal flow as assessed by colour Doppler ultrasound did not change significantly between day 1 (median 22 cm/s (15-35 cm/s)) and day 13 (median 19 cm/s (16-39 cm/s)).


CONCLUSIONS
A fourfold increase of urinary 6-beta-hydroxycortisol output after induction of cytochrome P-450 by rifampicin is associated with a significant but less than 10% increase in human liver volume. No increase of portal perfusion as assessed by Doppler ultrasound could be detected in this study.
Reichel
C
C
Department of General Internal Medicine, University of Bonn, Germany.
Block
W
W
Skodra
T
T
Träber
F
F
Schiedermaier
P
P
Spengler
U
U
Nuber
R
R
Schild
H H
HH
Sauerbruch
T
T
D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure; D008102:Liver Circulation; D008279:Magnetic Resonance Imaging; D008297:Male; D011168:Portal System / Q000502:physiology*; D011446:Prospective Studies; D012293:Rifampin / Q000494:pharmacology; D018709:Statistics, Nonparametric; D018617:Ultrasonography, Doppler, Pulsed
C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D012293:Rifampin; D006854:Hydrocortisone