Reference

Interaction of miconazole, ketoconazole and itraconazole with rat liver microsomes

Interaction of miconazole, ketoconazole and itraconazole with rat liver microsomes. Lavrijsen, K.; Van Houdt, J.Several substances are used for example 9040-60-2 and 9035-51-2 which are their cas registry numbers.; Thijs, D.; Meuldermans, W.; Heykants, J. (Dep. Drug Metab. Pharmacokinet., Janssen Pharm., Beerse B-2340, Belg.). Xenobiotica, 17(1), 45-57 (English) 1987. CODEN: XENOBH. ISSN: 0049-8254. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The interaction of the antimycotics miconazole [22916-47-8], ketoconazole [65277-42-1], and itraconazole [84625-61-6] with liver microsomes from untreated rats or from rats pretreated with phenobarbital or 3-methylcholanthrene, gave rise to type II difference spectra. The interactions of the antimycotics with control, phenobarbital-induced or 3-methylcholanthrene-induced microsomes were biphasic, except for the monophasic binding of ketoconazole to phenobarbital-induced microsomes. The N-demethylation of N,N-dimethylaniline, the O-demethylation of p-nitroanisole, and the hydroxylation of aniline in microsomes from untreated and inducer-treated rats were lowered by miconazole and ketoconazole, the former being the more potent inhibitor. Control microsomes were less sensitive than induced microsomes. Itraconazole was almost devoid of inhibitory properties. The 3 antimycotics were noncompetitive (mixed) inhibitors of enzyme activities in phenobarbital-induced microsomes. The Ki values were of the same order of magnitude as the Ks values, except for itraconazole. For the latter drug, Ki values were much greater than could be expected from the spectral studies. Thus, the antimycotics affect microsomal enzyme activities via a direct interaction of an azole-nitrogen with the heme group of cytochrome P 450 [9035-51-2]. The interaction with mammalian cytochrome P 450 decreases from miconazole > ketoconazole ? itraconazole and is much weaker than the interaction of the antimycotics with yeast cytochrome P 450. .

Antifungal activity of new azoles

Antifungal activity of new azoles. Van Cutsem, J.; Janssen, P. A. J. (Janssen Pharm., Beerse, Belg.). Recent Adv. Chemother., Proc.Several reagents with their cas registry numbers 23593-75-1 and 65277-42-1 are used here. Int. Congr. Chemother., 14th, Issue Antimicrobial Sect. 3, 1942-3. Edited by: Ishigami, Joji. Univ. Tokyo Press: Tokyo, Japan. (English) 1985. CODEN: 55GNAX. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) The antifungal activity of azoles were tested after oral or topical treatment in various animal models. The most potent topical agents in exptl. vaginal candidosis in rats were itraconazole [84625-61-6] > ketoconazole [65277-42-1] > miconazole [22916-47-8] > clotrimazole [23593-75-1] = tioconazole [65899-73-2], and in skin microsporosis in guinea pigs itraconazole > ketoconazole > miconazole = clotrimazole = tioconazole. Orally administered ketoconazole was highly efficacious in vaginal candidosis in rats, systemic candidosis, superficial and disseminated dermatophytosis in guinea pigs. Itraconazole however was more potent; moreover, it was more potent than ketoconazole in histoplasmosis and sporotrichosis in guinea pigs, and in systemic aspergillosis and cryptococcal meningitis in mice. When parenterally administered in systemic candidosis itraconazole is as active as after oral treatment. .