Urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids ratio as a measure of hepatic CYP3A4 capacity after enzyme induction.
BACKGROUND
The correlation between the urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids (6beta-OHF/17-OHCS) ratio and the metabolic capacity of the most abundant form of hepatic cytochrome P450 (CYP3A4) after induction remains unclear.


METHODS
Concentrations of 6beta-OHF and 17-OHCS in spot urine specimens obtained from 61 epileptic children receiving continuous carbamazepine therapy were measured by high-performance liquid chromatography. The relationship between the urinary 6beta-OHF/17-OHCS ratio and the serum carbamazepine concentration, corrected for dose and body weight, was examined.


RESULTS
Serum carbamazepine was inversely associated with the urinary 6beta-OHF/17-OHCS ratio, and the hyperbolic relationship between the two parameters was statistically significant (P < 0.01).


CONCLUSIONS
Carbamazepine is well known as a potent inducer and a substrate of hepatic CYP3A4. The present results suggest that measurement of the urinary 6betaOHF/17-OHCS ratio is helpful for assessing individuals' hepatic CYP3A4 capacity after enzyme induction.
Department of Hospital Pharmacy, Shiga University of Medical Science, Otsu, Japan. konishi@belle.shiga-med.ac.jp
Hiroki
H
Konishi
Kazuhiko
K
Tanaka
Tokuzo
T
Minouchi
Akira
A
Yamaji
D015065:17-Hydroxycorticosteroids / Q000652:urine*; D000293:Adolescent; D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D008099:Liver / Q000201:enzymology*; D008297:Male
D015065:17-Hydroxycorticosteroids; D002220:Carbamazepine; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006854:Hydrocortisone