Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The discovery of the antifungal activity of azole compounds represented an important therapeutic advance. Miconazole, ketoconazole, and fluconazole are currently commercially available, and itraconazole has undergone extensive clinical evaluation. Because of its limited activity and toxicity, miconazole has been replaced by newer agents. Ketoconazole has proven useful in therapy for superficial infections and invasive infections caused by the pathogenic fungi. Among its disadvantages are limited absorption in the absence of gastric acid and its potential for drug-drug interactions. Fluconazole is the only azole available as oral and intravenous preparations. Unlike other azoles, it is only minimally metabolized in the liver and largely excreted in the urine as active drug. It is more effective than ketoconazole against superficial candidal infections and is the drug of choice for maintenance therapy for cryptococcal meningitis in patients infected with human immunodeficiency virus. An advantage of itraconazole is its activity against aspergillosis. It is also active against many infections caused by pathogenic fungi. Other azole compounds are at varying stages of preclinical and clinical investigation.
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PMID:Azole antifungal agents. 131 5

Cryptococcus neoformans is an important opportunist pathogen in human immunodeficiency virus (HIV) infection. Cryptococcal meningitis (CM) 3rd after primary HIV neuropathy an Toxoplasma gondii among infectious neurological diseases in AIDS patients. Extrapulmonary infection due to C. neoformans has occurred in up to 13% of patients. 86% of the Cryptococcus spp isolates in the US, Canada, and Japan are serotype A. Thousands of infection due to var neoformans have been reported in AIDS patients but only 3 cases of var gattii. Cryptococcal pneumonia meningitis appears in 63-84% of AIDS patients with symptoms of fever, headache, meningism, and photophobia. 17-37% of AIDS patients with Cm die during therapy, and only 18-30% live over 12 months. Treatment in patients without immunodeficiency deficit is with a combination of .3 mg/kg/day of amphotericin B and 150 mg/kg/day of flucytosine for 4 weeks. A dose of .5-.8 mg/kg/day amphotericin was most effective although renal toxicity occurred in 80% of patients. Fluconazole has been used since 1987: cerebrospinal fluid concentrations reached 60-80% in serum. Treatment in 8 of 14 patients receiving 400 mg/day fluconazole failed while it did not in 6 patients treated with .7 mg/kg/day of amphotericin for 7 days and flucytosine 100 mg/kg/day. 200 mg/bid itraconazole was given to 32 patients with cryptococcosis (24 CM cases and 26 AIDS victims) and 65% of CM patients improved clinically with negative cultures. The relapse of 2 of 106 patients taking 200 mg/day fluconazole and 13 of 77 patients taking 1 mg/kg/week amphotericin B occurred in maintenance therapy. CM was suppressed in 10 of 15 patients with 400 mg/kg itrazonazole. Prophylactic use of azole drugs in AIDS does not protect completely from CM although it reduced systemic fungal infections such as cryptococcosis.
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PMID:Cryptococcal infection in AIDS. 161 62

We have reviewed the efficacy of the use of fluconazole in patients with definitely proven Candida esophagitis (CE) associated with human immunodeficiency virus (HIV) infection, using a single 400 mg oral dose of fluconazole and evaluating the patient three days afterwards. This drug showed to be effective for the clinical and endoscopic cure in all patients (100%), and with microbiological cure in ten cases. There was no clinical feature of toxicity. The only side effect was an increased alkaline phosphatase and transaminase activity without hyperbilirubinemia, but this finding was not statistically significant (p greater than 0.05). Fluconazole, given in a single 400 mg dose, was absolutely effective to cure esophagitis in AIDS, thus permitting to avoid parenteral amphotericin.
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PMID:[Candida esophagitis treated with a single dose of fluconazole in patients with HIV: presentation of 11 cases]. 209 54

Fluconazole pharmacokinetics, including absolute bioavailability, were determined for one group of controls (n = 10) and two groups of people with human immunodeficiency virus (HIV) infection (those with CD4+ T-cell counts of less than [n = 4] or greater than [n = 9] 200 cells per mm3). Twenty subjects received four doses of fluconazole; three doses were oral (50, 100, and 400 mg), and one dose was intravenous (either 50, 100, or 400 mg). The other three subjects received one or two doses. The groups were comparable in terms of the weight, body mass index, and estimated creatinine clearance of the subjects, but the people with HIV infection were older. Pharmacokinetic parameters indicated linearity in all subjects; the area under the plasma concentration-time curve and the maximum concentration increased in proportion to the dose. The fraction of an oral dose of fluconazole absorbed approximated unity in all three groups of subjects. The mean (+/- standard deviation) plasma clearance of fluconazole was lowest in the group of subjects with low CD4+ T-cell counts; the value for this group was 0.74 +/- 0.19 liter/h, compared with 0.97 +/- 0.19 liter/h in the group with HIV infection and CD4+ T-cell counts of greater than 200 cells/mm3 and 1.18 +/- 0.23 liter/h in the group of control subjects (P < 0.05). The volume of distribution was lower in those with HIV infection (P = 0.04, corrected for weight). The half-life was longest in people with HIV infection and low CD4+ T-cell counts (P = 0.01). This study has shown that some differences do exist between the pharmacokinetics of fluconazole in people with HIV infection and those in noninfected controls.
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PMID:Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. 748 28

The objective of this study was to determine the pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus (HIV) infection. After an overnight fast, a single dose of either 2 mg.kg-1 or 8 mg.kg-1 was administered in a suspension; five children received 2 mg.kg-1 and four 8 mg.kg-1 (ages 5-13 years). Blood samples were collected at various times on day 1, and once daily on days 2-7 after the dose. Fluconazole serum concentrations were measured by gas chromatography. At the dose of 2 mg.kg-1, the Cmax, AUC (0-infinity), and t1/2 ranged from 2.3-4.4 micrograms.ml-1, 84.9-136 micrograms.h.ml-1, and 19.8-34.8 h, respectively. At the dose of 8 mg.kg-1 the Cmax, AUC (0-infinity), and t1/2 ranged from 5.4-12.1 micrograms.ml-1, 330-684 micrograms h.ml-1, and 25.6-42.3 h, respectively. When compared with published data in healthy adults, fluconazole achieved similar serum concentrations in the present group of children, indicating a nearly complete degree of absorption.
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PMID:Pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus infection. 758 57

Fluconazole inhibits cytochrome P-450-mediated enzymatic metabolism of several drugs. Since hepatic metabolism is partially responsible for 2',3'-dideoxyinosine (didanosine or ddI) elimination, fluconazole therapy may lead to increased ddI concentrations in serum and subsequent concentration-dependent adverse effects. The purpose of this study was to determine if ddI pharmacokinetics are influenced by a 7-day course of oral fluconazole. Twelve adults with human immunodeficiency virus (HIV) who had received a constant dosage of ddI for at least 2 weeks were investigated. On study day 1, multiple serum samples for determination of ddI concentrations were obtained over 12 h. Then subjects received a 7-day course of oral fluconazole (200 mg every 12 h for two doses and then 200 mg once daily for 6 days) while ddI therapy continued. Following the last dose of fluconazole, serum samples for determination of ddI concentrations were again obtained over 12 h. ddI concentrations in serum were analyzed by radioimmunoassay. In contrast to previously published data, there was marked between-subject variability in ddI areas under the concentration-time curve, even when the dose was normalized for weight. No significant differences were found between mean ddI areas under the concentration-time curve from 0 to 12 h on study day 1 (1,528 +/- 902 ngx.hr/ml) and following fluconazole treatment (1,486 +/- 649 ngx.hr/ml) . There were no significant differences in other pharmacokinetic parameters, such as ddI peak concentrations in serum (971 +/- 509 and 942 +/- 442 ng/ml) or half-lives (80 +/- 32 and 85 +/- 21 min.) before and after fluconazole treatment, respectively. We conclude that a 7-day course of oral fluconazole does not significantly alter ddI pharmacokinetics in adults that are infected with human immunodeficiency virus.
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PMID:Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in persons seropositive for human immunodeficiency virus. 762 87

Thirty human immunodeficiency virus-positive patients carrying Candida albicans in their oropharynx were treated with fluconazole and were monitored for 90 to 570 days. Fluconazole-resistant C. albicans (MIC, > 32 micrograms/ml) appeared only in seven patients and only after 90 days of treatment corresponding to a total dose of more than 10 g. Resistance was not associated with resistance to other azole derivatives. Susceptible and resistant strains from each patient had the same genotype (as defined by electrophoretic karyotype and restriction fragment length polymorphism). Thus, the resistant strains were selected by the antimycotic treatment from the susceptible strain present in each case.
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PMID:Fluconazole-resistant recurrent oral candidiasis in human immunodeficiency virus-positive patients: persistence of Candida albicans strains with the same genotype. 802 27

The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days. Fluconazole coadministration decreased (P < .001) the apparent oral serum clearance of zidovudine by 43% and the apparent oral formation clearance to zidovudine glucuronide (GZDV) by 48%, resulting in increases (P < .002) in the area under the serum concentration time curve (74%), the maximum serum concentration (84%), and the terminal half-life (128%) of zidovudine. The molar ratio of GZDV to zidovudine recovered in urine was reduced by 34% with fluconazole (P < .001). These pharmacokinetic changes suggest that 400 mg of fluconazole inhibited the conversion of zidovudine to GZDV. Patients receiving this combination should be monitored for the development of zidovudine-related adverse reactions.
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PMID:Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. 759 35

Prosthetic arthritis due to Candida species is uncommon, with only 15 cases reported in the literature. We recently cared for a human immunodeficiency virus-infected patient who developed Candida parapsilosis prosthetic arthritis unresponsive to resection arthroplasty, intravenous amphotericin B, and suppressive ketoconazole therapy. Treatment with fluconazole led to mycologic cure and symptom improvement, although he subsequently underwent above-the-knee amputation due to continued joint instability. Fluconazole may be useful follow-up therapy after a course of amphotericin B combined with resection arthroplasty or when removal of the prosthesis cannot be accomplished.
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PMID:Candida prosthetic arthritis: report of a case treated with fluconazole and review of the literature. 842 Feb 85

Fluconazole and itraconazole MICs were determined by both the standard macrodilution method of the National Committee for Clinical Laboratory Standards and a colorimetric broth microdilution method for 140 isolates of Torulopsis (Candida) glabrata obtained over a 15-year period. Using the method of the National Committee for Clinical Laboratory Standards the MICs at which 90% of isolates are inhibited (MIC50) for all isolates were 32 and 1.6 micrograms/ml for fluconazole and itraconazole, respectively. For fluconazole, the MIC90 rose from 16 to > 64 micrograms/ml when the MIC90s for isolates collected from July 1980 to June 1991 were compared with those for isolates collected from July 1991 to March 1995. For itraconazole, the MIC90s for isolates from the same time periods were 0.8 and 3.2 micrograms/ml, respectively. Although for isolates from some non-human immunodeficiency virus-infected patients the MICs rose, most of the high MICs were found for isolates from human immunodeficiency virus-infected patients who had been extensively treated with azole drugs for thrush. The colorimetric method yielded endpoints that were more definitive; concordances within 2 dilutions for the two methods were 87% for fluconazole and 86% for itraconazole.
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PMID:Torulopsis glabrata: azole susceptibilities by microdilution colorimetric and macrodilution broth assays. 856 92


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