Effect of food and gastric acidity on absorption of orally administered ketoconazole.
Effects of food and gastric acidity on the bioavailability of ketoconazole tablets were investigated in 12 volunteers using a six-treatment, randomized, Latin-square crossover design. All volunteers received all treatments, as follows: (A) ketoconazole 200 mg administered after a fast; (B) ketoconazole 200 mg with a standardized high-fat meal; (C) ketoconazole 200 mg with a standardized high-carbohydrate meal; (D) ketoconazole 200 mg after pretreatment with glutamic acid hydrochloride 680 mg as capsules; (E) ketoconazole 200 mg in a simulated achlorhydric state induced with cimetidine and sodium bicarbonate; and (F) ketoconazole 200 mg administered with glutamic acid hydrochloride in a simulated achlorhydric state. Ketoconazole concentrations were measured by high-performance liquid chromatography in plasma samples drawn immediately before and at various times over 24 hours after drug administration. Bioavailability variables, including natural logarithm transformation for area under the concentration-time curve (AUC), were subjected to analysis of variance followed by Duncan's Multiple Range testing. Treatments B and C significantly prolonged the times required to achieve the peak plasma ketoconazole concentration, and treatment C also significantly reduced the peak plasma ketoconazole concentration (Cmax) compared with treatment A. There was a trend toward increased AUC values with treatment B and decreased AUC values with treatment C. Treatment D produced a higher Cmax compared with treatment A, and treatment E produced large, significant reductions in Cmax and AUC values compared with treatment A. Treatment F significantly increased AUC values and Cmax compared with treatment E.(ABSTRACT TRUNCATED AT 250 WORDS)
Lelawongs
P
P
College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08854.
Barone
J A
JA
Colaizzi
J L
JL
Hsuan
A T
AT
Mechlinski
W
W
Legendre
R
R
Guarnieri
J
J
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005502:Food; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D007654:Ketoconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013607:Tablets
D013607:Tablets; D007654:Ketoconazole