Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men.
OBJECTIVE
To determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs, and to assess the utility of the erythromycin breath test (ERMBT) to predict and explain these effects.


METHODS
Open-label, randomized, balanced, single-dose, three-period crossover study.


METHODS
University research center.


METHODS
Twelve healthy men.


METHODS
Subjects received amprenavir 1200 mg, ketoconazole 400 mg, and amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days.


RESULTS
Serial plasma samples for amprenavir and ketoconazole concentrations were measured by high-performance liquid chromatography. Coadministration of the drugs increased amprenavir area under the curve extrapolated to infinity (AUCinfinity) by 31% and reduced its maximum concentration (Cmax) by 16%. Amprenavir increased the AUCinfinity of ketoconazole by 44% and increased the drug's half-life and Cmax by 23% and 19%, respectively. Both agents resulted in substantial inhibition of ERMBT.


CONCLUSIONS
Coadministration of ketoconazole and amprenavir results in a statistically significant increase in AUC for both agents, but the changes are not likely to be clinically important.
Polk
R E
RE
Department of Pharmacy, Virginia Commonwealth University/Medical College of Virginia Campus, Richmond, USA.
Crouch
M A
MA
Israel
D S
DS
Pastor
A
A
Sadler
B M
BM
Chittick
G E
GE
Symonds
W T
WT
Gouldin
W
W
Lou
Y
Y
D000328:Adult; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics*; D001944:Breath Tests; D002219:Carbamates; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004917:Erythromycin / Q000032:analysis; D005663:Furans; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007654:Ketoconazole / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013449:Sulfonamides / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000935:Antifungal Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole