The effect of P-glycoprotein (Pgp) and/or CYP3A on the disposition of xenobiotics has been extensively investigated and is often of interest during drug discovery lead optimization. We have previously described a monkey pharmacokinetic screen to rapidly estimate absorption and first-pass extraction. In the present work, this monkey screen has been expanded to include an assessment of Pgp/CYP3A ...

Eight healthy adults were given single oral doses of ketoconazole (200, 400, 600, and 800 mg) in the fasting state and with a standard breakfast at weekly intervals according to a balanced block design. Concentrations in serum were measured up to 32 h after the dose. Food did not reduce ketoconazole absorption or significantly alter peak ketoconazole concentrations in serum, though there was a ...

The antifungal activity of orally active SM-4470, (R)-3-(n-butylthio)-2-(2,4-dichlorophenyl)-1-(imidazole-1-yl)-2-propanol hydrochloride, was compared with that of ketoconazole. SM-4470 showed twofold-higher activity than ketoconazole in the oral treatment of systemic infection with Candida albicans in mice. In addition, SM-4470 was effective against aspergillosis in mice, but ketoconazole was ...

INTRODUCTION Mifepristone, a competitive glucocorticoid receptor antagonist approved for Cushing syndrome, and ketoconazole, an antifungal and steroidogenesis inhibitor, are both inhibitors of and substrates for cytochrome P450 (CYP3A4). This study evaluated the pharmacokinetic effects of concomitant ketoconazole, a strong CYP3A4 inhibitor, on mifepristone. METHODS In an open-label, two-perio...

Preclinical and clinical data support the importance of signaling via the androgen receptor even in the setting of castration-resistant prostate cancer. However, the role of additional hormonal manipulations in patients progressing on cytotoxic chemotherapy has not been well defined. Recently, the novel lyase inhibitor, abiraterone acetate, has shown activity in patients with docetaxel-refracto...

Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has e...

The effect of ergosterol depletion by ketoconazole on the leishmanicidal activity of the pore-forming antibiotic amphotericin B (AmB) was investigated. Leishmania mexicana promastigotes were lysed within minutes by the addition of micromolar concentrations of AmB (0.5 microM) but became insensitive to AmB after growth in the presence of ketoconazole (0.25 microM, 90 h). Lipid chromatographic an...

Background: Acne vulgaris is a chronic inflammatory disease of pilosebaceous unit. The role of Pityrosporum ovale (P.ovale) in the exacerbation of acne is still under debate. Objective: To determine the efficacy of topical 2% ketoconazole cream in comparison to placebo in the treatment of acne vulgaris in patients with positive smear for P.ovale. Patients and Methods: A smear was obtained from ...

Drug hypersensitivity reactions are adverse reactions to drugs that were administered at a dose that is tolerated by normal subjects, but produce symptoms that, from a clinical perspective, resemble an allergy. The revised nomenclature for allergies classifies hypersensitivity reactions to drugs as either allergic or non allergic. Drug allergies occur when immunologic mechanisms have been demon...

BACKGROUND We previously found 70 mg flat-dose docetaxel coadministered with ketoconazole to modulate CYP3A4 to be the maximum tolerated dose that resulted in comparable docetaxel area under the plasma concentration-time curve (AUC) as 75-100 mg/m² docetaxel. PATIENTS AND METHODS We compared cycle 1 docetaxel pharmacokinetics and pharmacodynamics between ketoconazole-modulated (70 mg flat-dos...