Variability in activity of hepatic CYP3A4 in patients infected with HIV.
OBJECTIVE
To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in patients infected with the human immunodeficiency virus (HIV) using the erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to plasma concentrations of indinavir and nelfinavir.


METHODS
Prospective observational study.


METHODS
University infectious diseases clinic.


METHODS
Thirty-nine HIV-positive patients and 47 healthy controls.


METHODS
After the ERMBT in patients and controls, 25 patients received indinavir or nelfinavir.


RESULTS
Compared with controls, ERMBT variability was significantly greater in HIV-positive patients, including a subset of 19 patients receiving no concurrent drugs reported to alter CYP3A4 activity. Correlation between the ERMBT and first-dose plasma indinavir concentrations nearly reached statistical significance (p=0.07).


CONCLUSIONS
Variability in hepatic activity of CYP3A4 in HIV-positive patients may be greater than in controls and may explain some between-subject variability in plasma concentrations of indinavir. However, clearance mechanisms for protease inhibitors are complex, and if it is important to assess systemic exposure, the ERMBT is not a substitute for direct measurement of plasma concentrations.
Schools of Pharmacy, Virginia Commonwealth University, Richmond 23298-0533, USA.
D
D
Slain
A
A
Pakyz
D S
DS
Israel
S
S
Monroe
R E
RE
Polk
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001944:Breath Tests; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004917:Erythromycin; D015658:HIV Infections / Q000201:enzymology*; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D019888:Nelfinavir / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D019469:Indinavir; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019888:Nelfinavir