MCCONNELL SA, PENZAK SR, FINCHER TK, GURLEY BJ, FRANKS A, SACCENTE M, GUBBINS PO; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 28.
Univ. of Arkansas for Med. Sciences, Little Rock, AR
Purpose: To determine if there are sex-related differences in the pharmacokinetics of itraconazole (ITZ) and its hydroxyitraconazole (OHITZ) metabolite in healthy adult volunteers administered ITZ oral solution with either H[2]O or grapefruit juice (GFJ).METHODS: 20 subjects (10 male and 10 female) were studied in a randomized, open label crossover design with a 14-day washout period in-between each arm. Subjects were administered regular strength GFJ or H[2]O (240 mL) TID x 2 days, then ITZ oral solution 200mg x 1 dose with 240 mL of GFJ or H[2]O, followed by 240 mL of GFJ or H[2]O again, 2 hours later. Blood samples were obtained pre- and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72 hours post-dosing. Pharmacokinetic parameters for ITZ and OHITZ including C[max], T[max], apparent oral clearance (CL/F) and AUC[0-48]were determined. Pharmacokinetic data were compared between groups using a two-tailed, two sample Students T-test. Significance was defined as p<0.05.RESULTS: Significant differences in mean CL/F of ITZ were observed between males and females when ITZ was given with H[2]O, 0.647 +/- 0.0696 and 0.425 +/- 0.0333 L/hr/kg (p=0.008), respectively. However there were no significant sex-related differences observed in CL/F with ITZ when given with GFJ, 0.569 +/- 0.0908 and 0.387 +/- 0.0339 L/hr/kg (p=0.08), respectively. There were no other significant differences observed in pharmacokinetic ITZ parameters between sexes. Conclusion: There are significant sex-related differences in the CL/F of ITZ when given with H[2]O. However, the sex-related differences in the CL/F of ITZ are not observed when the ITZ is administered with GFJ in lieu of H[2]O.KEYWORDS: Grapefruit juice; Itraconazole
Publication Types:
Keywords:
- Adult
- Area Under Curve
- Beverages
- Cross-Over Studies
- Female
- Humans
- Itraconazole
- Male
- Protons
- Sex Characteristics
- hydroxyitraconazole
Other ID:
UI: 102248552
From Meeting Abstracts