Impact of amphotericin B on the cytochrome P450 system in HIV-infected patients.
OBJECTIVE
To investigate whether cytochrome P450-dependent enzymes are influenced by amphotericin B (Am-B) during the treatment of Candida oesophagitis in HIV-infected patients.


METHODS
Twelve HIV-infected, antiretroviral-naive patients (CDC/WHO stage C3) with Candida oesophagitits were enrolled into a prospective clinical trial. The patients were treated with Am-B (0.4 mg/kg body weight) for two weeks. At baseline and after Am-B therapy the clearance of antipyrine and its metabolites were investigated by high-performance liquid chromatography. In addition, the urinary excretion of 6-beta-hydroxycortisol and 17-hydroxycorticosteroids was assessed by means of a radioimmunoassay.


RESULTS
The following significant changes were observed after Am-B treatment (P < 0.01): increase of antipyrine half-life (12.4 h vs 16.8 h) and the area under the plasma concentration-time curve (27.9 mg min/ml vs 38.1 mg min/ml); decrease of the total body clearance (61.2 ml/min vs 43.7 ml/min); decrease of the renal clearance of antipyrine metabolites - norantipyrine (7.45 ml/min vs 5.31 ml/min), 4-hydroxyantipyrine (15.4 ml/min vs 10.3 ml/min), hydroxymethylantipyrine (4.31 ml/min vs 3.65 ml/min); decrease of urinary 6-beta-hydroxycortisol excretion (453 microg/24h vs 298 microg/24h) and the ratio of 6-beta-hydroycortisol to 17-hydroxycorticosteroids (8.8% vs 6.4%).


CONCLUSIONS
Our data indicate that Am-B therapy has an inhibitory effect on cytochrome P450-dependent enzymes in HIV-infected patients. These results are of particular significance for HIV-infected patients who are concomitantly treated with drugs that are predominantly metabolised in the liver. A careful drug monitoring system seems advisable, especially for proteinase inhibitor experienced HIV-1-infected subjects.
Brockmeyer
Norbert H
NH
Department of Dermatology, Ruhr-University Bochum, Gudrunstr, Germany. n.brockmeyer@derma.de
Gambichler
T
T
Bader
A
A
Kreuter
A
A
Kurowski
M
M
Sander
P
P
Altmeyer
P
P
D015065:17-Hydroxycorticosteroids / Q000652:urine; D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000201:enzymology* / Q000652:urine; D000666:Amphotericin B / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000983:Antipyrine / Q000493:pharmacokinetics; D002177:Candidiasis / Q000150:complications; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004941:Esophagitis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D016867:Immunocompromised Host
D015065:17-Hydroxycorticosteroids; D000900:Anti-Bacterial Agents; C001380:6 beta-hydroxycortisol; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine; D006854:Hydrocortisone