Ketoconazole

Publication Title: 
Biological & Pharmaceutical Bulletin

Candida albicans is one of the most prevalent human opportunistic pathogens. C. albicans undergoes a yeast-to-hyphal transition that has been identified as a virulence factor as well as a critical element for mature biofilm formation. A previous study in our lab showed retigeric acid B (RAB), a lichen derived pentacyclic triterpenoid, displayed synergistic antifungal activity with azoles. We now showed that this combination also proved to be adequate in combating the formation of hyphae in vitro.

Author(s): 
Chang, Wenqiang
Li, Ying
Zhang, Li
Cheng, Aixia
Liu, Yongqing
Lou, Hongxiang
Publication Title: 
Archives Internationales De Pharmacodynamie Et De Thérapie

The interaction of four imidazole antimycotics clotrimazole, econazole, ketoconazole and miconazole with other drugs was studied in in vivo models known to reveal inhibition and induction of microsomal enzymes. In rats the duration of methohexital hypnosis and the prothrombin time prolongation induced by acenocoumarol were changed after oral administration of all four antimycotics. The oral ED50-values of miconazole, econazole and clotrimazole for prolongation of methohexital hypnosis in female rats (acute inhibiton of microsomal enzymes) were 3.55, 3.56 and 10.7 mg/kg.

Author(s): 
Niemegeers, C. J.
Levron, J. C.
Awouters, F.
Janssen, P. A.
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Ro 42-1611 (arteflene) is a synthetic endoperoxide antimalarial. The antimalarial activity of endoperoxides is attributed to iron(II)-mediated generation of carbon-centered radicals. An alpha, beta-unsaturated ketone (enone; 4-[2',4' bis(trifluoromethyl)phenyl]-3-buten-2-one), obtained from arteflene by reaction with iron(II), was identified previously as the stable product of a reaction that, by inference, also yields a cyclohexyl radical. The activation of arteflene in vivo has been characterized with particular reference to enone formation.

Author(s): 
Bishop, L. P.
Maggs, J. L.
O'Neill, P. M.
Park, B. K.
Publication Title: 
British Journal of Clinical Pharmacology

AIMS: The study aimed to identify the specific human cytochrome P450 (CYP450) enzymes involved in the metabolism of artemisinin. METHODS: Microsomes from human B-lymphoblastoid cell lines transformed with individual CYP450 cDNAs were investigated for their capacity to metabolize artemisinin. The effect on artemisinin metabolism in human liver microsomes by chemical inhibitors selective for individual forms of CYP450 was investigated.

Author(s): 
Svensson, U. S.
Ashton, M.
Publication Title: 
British Journal of Clinical Pharmacology

AIMS: To evaluate whether the potent CYP3A4 inhibitor ketoconazole has any influence on the pharmacokinetic and electrocardiographic parameters of the antimalarial co-artemether (artemether-lumefantrine) in healthy subjects. METHODS: Sixteen subjects were randomized in an open-label, two period crossover design study. Subjects received a single dose of co-artemether (day 1) either alone or in combination with multiple oral doses of ketoconazole (400 mg on day 1 followed by 200 mg o.d. for 4 additional days).

Author(s): 
Lefèvre, Gilbert
Carpenter, Polly
Souppart, Claire
Schmidli, Heinz
McClean, Mark
Stypinski, Daria
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Emergence of drug-resistant Plasmodium falciparum strains to conventional first-line antimalarial drugs has compelled many countries to reorient their drug policies to adopt artemisinin-based combination therapies (ACTs) for treatment of uncomplicated malaria. This has increased the demand of artemisinin, already a scarce commodity. Synthesis of artemisinin is not yet commercially viable. Extensive use of available ACTs will invariably lead to emergence of resistance to these combinations.

Author(s): 
Mishra, Lokesh C.
Bhattacharya, Amit
Bhasin, Virendra K.
Publication Title: 
Oncotarget

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications.

Author(s): 
Kast, Richard E.
Boockvar, John A.
Brüning, Ansgar
Cappello, Francesco
Chang, Wen-Wei
Cvek, Boris
Dou, Q. Ping
Duenas-Gonzalez, Alfonso
Efferth, Thomas
Focosi, Daniele
Ghaffari, Seyed H.
Karpel-Massler, Georg
Ketola, Kirsi
Khoshnevisan, Alireza
Keizman, Daniel
Magné, Nicolas
Marosi, Christine
McDonald, Kerrie
Muñoz, Miguel
Paranjpe, Ameya
Pourgholami, Mohammad H.
Sardi, Iacopo
Sella, Avishay
Srivenugopal, Kalkunte S.
Tuccori, Marco
Wang, Weiguang
Wirtz, Christian R.
Halatsch, Marc-Eric
Publication Title: 
Phytomedicine: International Journal of Phytotherapy and Phytopharmacology

Holy basil, Ocimum sanctum (L.) is time-honored for its medicinal properties; however its antimicrobial characteristics are used only in 'Ayurvedic medicines'. Attention has been drawn to antifungal activity and a possible synergistic antifungal effect of Ocimum sanctum essential oil (OSEO) and established azole antimycotics-fluconazole and ketoconazole. To put forward this approach, antifungal activity has been assessed in seventy four fluconazole-sensitive and sixteen fluconazole-resistant Candida isolates.

Author(s): 
Amber, K.
Aijaz, A.
Immaculata, X.
Luqman, K. A.
Nikhat, M.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Oxycodone undergoes N-demethylation to noroxycodone and O-demethylation to oxymorphone. The cytochrome P450 (P450) isoforms capable of mediating the oxidation of oxycodone to oxymorphone and noroxycodone were identified using a panel of recombinant human P450s. CYP3A4 and CYP3A5 displayed the highest activity for oxycodone N-demethylation; intrinsic clearance for CYP3A5 was slightly higher than that for CYP3A4. CYP2D6 had the highest activity for O-demethylation. Multienzyme, Michaelis-Menten kinetics were observed for both oxidative reactions in microsomes prepared from five human livers.

Author(s): 
Lalovic, Bojan
Phillips, Brian
Risler, Linda L.
Howald, William
Shen, Danny D.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

The role of P-glycoprotein (P-gp) on the distribution of the benzodiazepine triazolam (TRZ) and the azole antifungal agent ketoconazole (KET), and on the TRZ-KET interaction, was studied using mdr1a(-) or mdr1a/b(-/-) mice (P-gp-deficient mice) and matched controls. TRZ and KET also were studied in Caco-2 cells in Transwell culture. After single i.p. injections of TRZ or KET in separate groups of control mice, brain concentrations of TRZ exceeded those in serum [brain/serum area under the concentration curve (AUC) ratio, 5.0], whereas brain/serum AUC ratios for KET were approximately 0.5.

Author(s): 
von Moltke, Lisa L.
Granda, Brian W.
Grassi, Jeffrey M.
Perloff, Michael D.
Vishnuvardhan, Daesety
Greenblatt, David J.
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