The disposition of ketoconazole was characterized in the rat over a wide dose/concentration range. Bolus dose (0.03-10 mg/kg) studies indicate that plasma concentration-time profiles for ketoconazole are not superimposable when dose normalized because of nonlinearities occurring in both volume of distribution and clearance. The volume of distribution decreases from 3 to less than 1 L/kg, while the plasma clearance decreases 10-fold from 25 mL/min/kg as the dose is escalated. From these results, infusion rates were calculated to maintain the plasma concentrations achieved with particular bolus doses. The curvilinear relationship between steady-state plasma concentration (0.015-8.3 mg/L) and ketoconazole infusion rate (0.021-2.45 mg/hr/kg) was analyzed in terms of Michaelis-Menten kinetics. A Vmax of 3.2 mg/hr/kg and Km of 2.1 mg/L were obtained by nonlinear regression analysis. At the end of the ketoconazole infusion, liver, adrenals and kidneys were removed and assayed for ketoconazole. Tissue-to-plasma partition coefficients for the liver and adrenals showed a marked dependence upon steady-state plasma concentration. Both parameters (liver, 22; and adrenals, 53) showed a decrease of approximately 10-fold as the plasma concentrations were increased. In contrast, the kidney:plasma partition coefficient (1.8), blood:plasma concentration ratio (0.6), and plasma binding (96%) of ketoconazole did not show a concentration dependence over the range studied. It is concluded that the liver is an important determinant of ketoconazole's volume of distribution and that saturation of this process accounts largely for the reduction in volume of distribution with increasing dose.(ABSTRACT TRUNCATED AT 250 WORDS)
nizoral cream generic
To improve our understanding of the prescribing and patient-monitoring practices of physicians prescribing medications with a BBW to patients age >or=65 years in an ambulatory care setting.
Two experimental approaches were used: (i) blockade of CYP3A4 metabolism by coadministration of ketoconazole to increase the plasma concentrations of the parent compound in the conscious guinea-pig, and (ii) administration of the compound directly into the coronary circulation of the anaesthetised dog in order to circumvent first-pass metabolism.
nizoral generic name
With the availability of more number of antifungal agents in recent years, drugs other than saturated solution of potassium iodide (SSKI) are being increasingly used to treat sporotrichosis. It was therefore considered pertinent to evaluate in vitro antifungal susceptibility pattern of Sporothrix schenckii strains isolated at three centers in India against five commonly used antifungal agents.
online buy nizoral
The effect of several imidazole containing drugs including keto on human adrenal 17 alpha-hydroxylase, 17,20-lyase, 21-hydroxylase, 11 beta-hydroxylase and 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) activities was studied in vitro. The order of decreasing inhibitory potency as determined from ID50 values for both 17 alpha-hydroxylase (ID50 values ranged from 1.13-4.17 mumol/l) and 17,20-lyase (0.57-1.95 mumol/l) activities was: bifon greater than clot greater than keto greater than micon greater than econ greater than isocon greater than tiocon. Using [3H]progesterone (5.50-12.25 mumol/l) as the substrate for the 21-hydroxylase activity the order of decreasing inhibitory potency was: clot greater than bifon greater than isocon greater than micon greater than tiocon greater than econ greater than tiocon greater than keto. For the 11 beta-hydroxylation of [3H]deoxycortisol (1.48-2.34 mumol/l) the order of decreasing inhibitory potency was keto greater than bifon greater than clot greater than micon greater than econ greater than isocon greater than tiocon. The cytochrome P-450 dependent enzyme most sensitive to inhibition was 17,20-lyase and the least sensitive was 21-hydroxylase whereas the imidazole drugs were without effect on the cytochrome P-450 independent 3 beta-HSD-I activity. In agreement with previous results a common structural feature of the imidazole drugs having an inhibitory effect was the presence of aromatic rings on the N-1 substituent of the imidazole ring.
nizoral generic shampoo
Seborrhoeic dermatitis is a common entity that conventionally is difficult to treat. Recently, topical ketoconazole has been proven successful. To determine if other azoles, and in particular the more modern ones, are also helpful in this condition, a double-blind multicentre randomized controlled trial was performed in patients suffering from seborrhoeic dermatitis involving individuals 16 years and older without human immunodeficiency virus (HIV) infection. One hundred patients were enrolled and treated according to a random plan with either bifonazole 1% cream or the corresponding vehicle once daily for 4 weeks. All patients were evaluated at the beginning of the study, as well as after 2 and 4 weeks, i.e. the treatment period proper, and after 6 weeks of follow-up. Clinical evaluation was based on scores of 0-3 for the following parameters: erythema, papules, infiltration, scaling, itch. In addition, mycological evaluation was performed using adequate contact plates for quantitative determination of Malassezia furfur. In the end, 92 patients were at least partially evaluable. In general, the verum preparation tended to be more efficacious, e.g. the score for erythema amounted to 0.75 after 4 weeks as compared with 0.88 in the control group, the baseline values being 2.18 and 2.04 respectively. With itch, the corresponding figures were 0.17 and 0.33 as compared with 1.42 and 1.38 before treatment. While in statistical terms there was significant difference in these parameters, such a difference was demonstrated by clinical judgement at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
nizoral pills buy
Serum lactate dehydrogenase (LDH) isoenzyme activity was analyzed in cetaceans. Animals that were treated by i.m. injection and others that received azole therapy had distinctly different LDH isoenzyme profiles. A third distinctive pattern was occasionally observed in clinically normal animals with elevations in total transaminase and LDH activity levels. DH isoenzyme activity patterns were not affected by mild or moderate hemolysis, refrigeration after 24 hr, or freezing for 24 hr with subsequent thawing. However, severe hemolysis produced artifactual changes similar to those observed in individuals that received injections but of a lesser magnitude. DH isoenzyme activity patterns may provide useful corroboration of other clinical findings when diagnostic modalities are limited, especially to differentiate nonspecific enzyme elevation from nonpathologic elevations in serum enzyme concentrations due to i.m. injections or azole therapy.
nizoral tablets buy
Guinea pigs and athymic nude (RNU/RNU) rats were used to assess the efficacy of three orally administered antifungal agents--Tolciclate, Tolnaftate, and Ketoconazole--against Trichophyton mentagrophytes dermatophytosis. All three antifungal agents inhibited the test strain of T. mentagrophytes in vitro. Antifungal agents were tested in intervention (oral therapy started 5 days after challenge) or prophylaxis (oral therapy started 5 days before challenge) protocols. Oral treatment of dermatophytosis on guinea pig skin demonstrated that Tolciclate and Tolnaftate alleviated clinical symptoms and shortened the duration of the dermatophytosis, in comparison to nontreated controls. Assessment of antifungal efficacy in the guinea pig model was time consuming (30-35 days) and variability in the duration and severity of clinical symptoms on guinea pig skin was common. Oral therapy of chronically infected athymic rats demonstrated that Tolciclate, Tolnaftate, and ketoconazole were effective antifungal agents in vivo. Obvious improvement in clinical symptoms of dermatophytosis (i.e. less erythema and fewer lesions) was evident with all three antifungal agents within 10 days of starting oral therapy. By day 20, athymic rats that were treated with either Tolciclate or Ketoconazole showed marked clinical improvement of the chronic dermatophytosis. Chronically infected athymic rats, which lack thymus matured T-cells, are a promising new model to evaluate the efficacy of antifungal agents by culture, histology, and visual observations of clinical symptoms.
At doses similar to those used for clinical treatment, voriconazole showed lower antifungal activity in experimental rat paracoccidioidomycosis than that obtained with itraconazole and sulfamethoxazole-trimethoprim.