Disease relevance of Nizoral

• It appears that maintenance prophylactic therapy with oral ketoconazole is effective in preventing recurrent episodes of vulvovaginal candidiasis, but that relapse is common after withdrawal of the drug [1].
• Ketoconazole in the management of precocious puberty not responsive to LHRH-analogue therapy [2].
• Candidal epididymitis treated with ketoconazole [3].
• Transient, asymptomatic cholestasis was observed in the ketoconazole group [4].
• Reversible adrenal insufficiency induced by ketoconazole [5].

Psychiatry related information on Nizoral

• CONCLUSIONS: These findings suggest that late onset CAH can contribute to anxiety disorders and that adrenal suppressive therapy or inhibition of steroidogenesis with ketoconazole may be efficacious as adjuvant therapy [6].
• Depressive and withdrawal symptoms improved no more with ketoconazole than with placebo treatment, and side effects were greater on ketoconazole than placebo [7].
• Several factors including decreased physical activity, total body magnesium depletion, and intermittent ketoconazole and short-term prednisone treatment, may have contributed to the development and progression of osteoporosis [8].
• While griseofulvin has been used for more than four decades, the use of early azoles, such as ketoconazole have resulted in better patient compliance and thus greater success [9].
• Our preliminary findings suggest that ketoconazole may be useful in some patients with bipolar depression [10].

High impact information on Nizoral

• Because ketoconazole can markedly reduce the need for cyclosporine and because it also has antimicrobial properties, it may offer benefits in the treatment of patients after cardiac transplantation [4].
• This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone [11].
• Disseminated intravascular coagulation in prostatic carcinoma reversed by ketoconazole [12].
• Failure of ketoconazole in cryptococcal meningitis [13].
• A combination of a differentiation-inducing deltanoid with a compound that blocks entry of calcium into cells (e.g., ketoconazole) may offer a new approach to differentiation therapy and address the problem of hypercalcemia [14].

Chemical compound and disease context of Nizoral

• Our approach was to assess the ability of three drugs: ketoconazole, clotrimazole, and RS 49910, to inhibit [3H]dexamethasone binding to hepatoma tissue culture (HTC) cell cytosol [15].
• The cure rate in these patients suggests that ketoconazole may replace amphotericin B as the initial treatment of blastomycosis that is not overwhelming [16].
• Relapse of Candida parapsilosis endocarditis after long-term suppression with flucytosin: retreatment with valve replacement and ketoconazole [17].
• When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats [18].
• Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583) [19].

Biological context of Nizoral

• Following continuous oral treatment, the mean day 28 AUC for all-trans RA was significantly lower than that on day 1 (213 ng/mL per hour versus 467 ng/mL per hour; P < .01), a decline significantly attenuated by ketoconazole, which increased the mean plasma all-trans RA AUC on day 29 to 375 ng/mL per hour (P < .01) [20].
• PURPOSE: We studied the clinical pharmacology of all-trans RA in cancer patients to determine possible mechanisms of acquired resistance and evaluated the potential for reversal by ketoconazole, an inhibitor of cytochrome-P450 oxidative enzymes [20].
• Ketoconazole-deltanoid combinations produced only minor changes in intracellular calcium homeostasis compared with changes produced by 1,25-dihydroxyvitamin D3, either alone or in combination with ketoconazole [14].
• CONCLUSIONS: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria [21].
• The binding of two molecules of ketoconazole to the CYP3A4 active site and the clear indication of multiple binding modes for erythromycin has implications for the interpretation of the atypical kinetic data often displayed by CYP3A4 [22].

Anatomical context of Nizoral

• In cultured hepatocytes conversion of [4-14C]cholesterol into bile acids was dose dependently reduced by the antimycotic drug ketoconazole, giving half-maximal inhibition at 10 microM ketoconazole in rat hepatocytes and at 1 microM in human hepatocytes [23].
• Ketoconazole binds to glucocorticoid receptors and exhibits glucocorticoid antagonist activity in cultured cells [15].
• When patients who had received allogeneic bone-marrow transplant were studied separately, there was no significant difference between the two treatments, probably because there was a fall-off in ketoconazole absorption from the end of the third week after the transplant [24].
• The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy [25].
• High-dose ketoconazole for treatment of fungal infections of the central nervous system [25].

Associations of Nizoral with other chemical compounds

• 18 renal transplant recipients receiving cyclosporin, prednisone, and azathioprine were given ketoconazole, a potent inhibitor of the cytochrome P-450 enzyme system [26].
• Increased gastric pH and the bioavailability of fluconazole and ketoconazole [27].
• Chemotherapy was attempted with various regimens including oral ketoconazole, intravenous or intraperitoneal amphotericin B, and oral flucytosine [28].
• Relative to Ringer's, indomethacin had no effect, BW755c caused vasodilation, and ketoconazole caused vasoconstriction, which suggests that cytochrome P450 products might be vasoactive mediators in injured tissue [29].
• At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70% [30].
• Because loss of PXR maintains blood levels of paclitaxel upon chronic dosing, ketoconazole analogues may also serve to preserve paclitaxel blood levels on chronic dosing of drugs [31].
• Ketoconazole decreased R-138727 and clopidogrel active metabolite Cmax (maximum plasma concentration) 34-61% after prasugrel and clopidogrel dosing [32].
• We show that the CYP3A5*1/*3 polymorphism is an important determinant of the response to inhibition of tacrolimus metabolism by ketoconazole, with a 30% greater inhibition in those lacking *1 allele [33].
• The response proportion to ketoconazole, hydrocortisone, and dutasteride was at least comparable with previous studies of ketoconazole alone, whereas time to progression was substantially longer [34].

Gene context of Nizoral

• Specifically, CYP26C1 can also recognize and metabolize 9-cis-RA and is much less sensitive than the other CYP26 family members to the inhibitory effects of ketoconazole [35].
• Production of APC, NPC, M2, and M4 was prevented by ketoconazole, a specific CYP3A inhibitor [36].
• CONCLUSIONS: These results show that ketoconazole is a potent UGT1A1 inhibitor, which seems the basis for increased exposure to SN-38 when coadministered with irinotecan [37].
• In the current study, we investigated the effect of ketoconazole and other azole-derived drugs, miconazole and fluconazole, on the transcriptional activity of the human GR (hGR) in HeLa and HepG2 cells, and in primary human hepatocytes [38].
• Among the UGT1A isoforms screened, ketoconazole showed the highest inhibitory effect on UGT1A1 and UGT1A9 [37].

Analytical, diagnostic and therapeutic context of Nizoral

• We randomly assigned 43 patients at the time of cardiac transplantation to receive ketoconazole (200 mg per day) (23 patients) or no ketoconazole (20 patients) [4].
• In the first year, 22 percent of the ketoconazole group required cytolytic therapy, as compared with 35 percent of the controls, and 9 percent of the ketoconazole group required total lymphoid irradiation, as compared with 15 percent of the controls (P = 0.07) [4].
• Acute hypoadrenalism and hepatotoxicity after treatment with ketoconazole [39].
• Modified response to ketoconazole of Candida albicans from a treatment failure [40].
• Ketoconazole and fungal CAPD peritonitis [41].

References