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)

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few examples of well-documented clinically significant interactions include interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or digoxin, verapamil hydrochloride, human immunodeficiency virus-related protease inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent reports have demonstrated clinically relevant interactions with numerous other drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin, propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Enhanced knowledge of known interactions will continue to develop, including research on the induction of specific cytochrome P-450 isoenzymes and on the importance of the P-glycoprotein transport system. New rifampin and rifabutin interactions will be discovered with further investigations.
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PMID:Rifampin and rifabutin drug interactions: an update. 1199 7

An influence of splenin and its non-peptide factor of splenin (NFS) on the state of cytochrome P-450 dependent monooxygenase system (MOS) of liver microsomes in healthy animals under immunodeficiency (splenectomy, administration of gamma-aminobutyric acid (GABA) and toxic hepatosohepatitis was studied. The stimulating action of splenin and NFS on cytochrome P-450 content and MOS activity of liver microsomes in healthy animals has been established. The indices studied markedly decreased after splenectomy. The splenin or NFS administrations promote the recovery of these indices up to starting level in asplenic animals. A decrease in thymic mass dependent in GABA administration is prevented by NFS pretreatment of animals; there is no any effect of mediator acid on cytochrome P-450 content and MOS activity was noted. The preliminary administration NFS potentiates hepatotoxic effect of carbon tetrachloride and increases its inhibitory effect on P-450 dependent MOS of liver microsomes. Under the NFS action the effect in activity of the last is caused by the factor influence on the reparative processes in the liver.
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PMID:[Role of splenin and its active factor in regulating liver monooxygenase system in experimental immunodeficiency and hepatosohepatitis]. 1203 37

The number of people infected with human immunodeficiency virus (HIV) is gradually increasing in Japan, and the morbidity rate from tuberculosis in the Japanese people is high. Accordingly, the number of cases with both infections is considered to increase in the future. Our hospital has already encountered 31 cases of HIV associated tuberculosis. HIV infects mainly CD4-positive cells. The extreme decrease in the cell count results in serious cellular immunological disorder. CD4-positive cell disorder induces disorders of B lymphocytes, cytotoxic T cells, natural killer cells, and macrophage functions. These destructive conditions show the state of immunodeficiency including macrophage that are most important for defense of acid-fast bacterial infection. Migration and activation of macrophages with cytokines derived from T cells are impaired to induce the following phenomena: hypoplasia of granuloma, failure of tubercule bacillus suppression, the spread to regional lymph nodes (hilar or mediastinal lymph nodes), and hematogenous dissemination. On this occasion, caseous necrosis and cavitation are unlikely to occur, and false-negative tuberculin reaction is often observed. The incidence of severe cases, which include miliary tuberculosis, tuberculous meningitis, etc., and extrapulmonary tuberculosis, are high among acquired immunodeficiency syndrome (AIDS)-associated tuberculosis cases. HIV-infected tuberculosis cases are generally regarded as endogenous exacerbation, but they include primary infection and reinfection as well. Even during the treatment for drug-sensitive strains particularly, some cases may have reinfection with multidrug-resistant bacteria, suggesting that caution should be taken against this point. Conversely, the association of tuberculosis is a factor for the poor prognosis of HIV infection, since it facilitates the development of HIV infection. If the bacteria belong to a drug-sensitive strain, the infection with them responds well to antituberculous drugs, the same as in tuberculosis cases without HIV infection, showing a favorable prognosis. However, the mortality rate of infection with multi-drug-resistant tuberculosis is extremely high. The combined use of a protease inhibitor, i.e., anti-HIV drug, with rifampicin is regarded as contraindication for the treatment because rifampicin strongly induces hepatic cytochrome P-450 and increases the metabolism of protease inhibitors and nonnucleoside reverse transcriptases to markedly decrease the blood concentrations. Accordingly, the treatment for tuberculosis should take priority over that for HIV infection in HIV-infected tuberculosis, and highly active antiretroviral therapy (HAART) may be administered after the treatment of tuberculosis. When HAART is necessary for the treatment during the tuberculosis treatment, rifampicin had better be exchanged to rifabutin because the effect of rifabutin to induce cytochrome P-450 is less potent than that of rifampicin. A report has recently shown that the exacerbation of pyrexia and chest X-ray findings was transiently observed approximately 2 weeks after potent anti-HIV therapy for HIV-infected tuberculosis, which included a protease inhibitor. The reason for the exacerbation has been believed to be that the impaired function of CD4-positive cells is improved by the administration of anti-HIV drugs to raise temporarily the reaction of the vital part to M. tuberculosis. A tuberculin skin test (TST) reaction size of > or = 5 mm of induration is considered positive (i.e., indicative of M. tuberculosis infection) in persons who are infected with HIV. Persons with a TST reaction size > or = 5 mm who have not previously received treatment for M. tuberculosis infection should receive tuberculosis preventive treatment. Prevention by BCG vaccination is regarded as contraindications for HIV-infected patients, because disseminated M. bovis infection may be associated with them. Many HIV-positive patients infected with tuberculosis show uneventful healing, when M. tuberculosis is the sensitive strain. However, since some patients show the rapid course of tuberculosis, clinical physicians keep the early detection of tuberculosis for HIV-infected patients and the association of HIV infection for tuberculosis patients in their mind, respectively.
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PMID:[HIV infection and tuberculosis]. 1265 6

The purpose of this study was to evaluate in vitro interactions of commercially obtained pure herbal constituents with p-glycoprotein P-gp and cytochrome P-450 3A4 (CYP3A4) activities, which can further modulate the transcellular transport and metabolism kinetics of orally administered drugs. Caco-2 cells grown in the presence of 0.25 micromol/L 1alpha,25-dihydroxy vitamin D3 and multidrug-resistant 1 (MDR1) transfected MDCK cells were used as models to evaluate the effect of purified herbal constituents (quercetin, hypericin, hyperforin from St. John's wort, kaempferol from ginseng, silibinin from milk thistle, and allicin from garlic) on P-gp-mediated efflux of the human immunodeficiency virus (HIV) protease inhibitor ritonavir. In addition, the inhibitory effect of these constituents on CYP3A4-mediated metabolism was determined by using cortisol as a model compound. Silibinin and hyperforin did not significantly alter cellular uptake of H-ritonavir in Caco-2 cells. A similar result was also observed for silibinin when tested in MDR1-MDCK cells. Quercetin, hypericin, and kaempferol exhibited a remarkable inhibition of P-gp-mediated efflux of ritonavir by increasing its cellular uptake in these models. These values were also comparable with the inhibitory effect of quinidine in Caco-2 cells, a well-known inhibitor of P-gp, on ritonavir efflux from Caco-2 cells. Allicin exhibited a concentration-dependent inhibition of ritonavir efflux when tested on MDR1-MDCK cells. There was a significant decrease in the Apical to Basal/Basal to Apical (AP-BL/BL-AP) transport ratio of ritonavir in presence of hypericin, kaempferol, and quercetin. These herbal constituents inhibited the CYP3A4 activity when tested with the Vivid CYP3A4 assay kit, whereas silibinin did not alter cortisol metabolism. Hypericin showed a significant inhibition in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent metabolism of cortisol with 64.6% of intact drug at the end of a 1-hour study. Similarly, kaempferol and quercetin also caused substantial inhibition of cortisol metabolism with 89.7% and 90.1% of intact cortisol, respectively, compared with 45.9% in the control. Prolonged exposure of quercetin resulted in significant increase of mRNA expression of both MDR1 and CYP3A4 levels in Caco-2 cells. However, hyperforin caused upregulation of CYP3A4 and downregulation of MDR1, whereas the effect of silibinin and kaempferol remained inconclusive on these gene expressions. Hypericin, kaempferol, quercetin, and allicin inhibit the efflux and CYP3A4-mediated metabolism of xenobiotics in vitro. Hence, this study warns against the use of herbal constituents along with prescribed HIV protease inhibitors that are substrates for P-gp and/or CYP3A4.
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PMID:In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. 1526 18

Penicillium marneffei is a dimorphic fungus endemic in southeast Asia. The incidence of P. marneffei infection has increased greatly in this region with the spread of human immunodeficiency virus, but the infection routes and pathogenic mechanisms of P. marneffei remain poorly understood. P. marneffei is an opportunistic human pathogen exhibiting a temperature-dependent dimorphic switch. At 25 degrees C it grows as filamentous hyphae, whilst at 37 degrees C it forms uninucleate yeast cells and divides by fission. Dimorphic fungal pathogenicity is frequently associated with the dimorphic switch, but the mechanism that regulates the switch has remained obscure. In this report, two-dimensional difference gel electrophoresis was used to investigate the proteins expressed differentially in the yeast and mycelial phases of a wild-type isolate of P. marneffei. Among thousands of protein molecules displayed, more than 500 showed differential expression between the two phases. In particular, 26 proteins were identified using matrix-assisted laser desorption/ionization time-of-flight MS. Expression of catalase-peroxidase, isocitrate lyase, Hsp90, binding protein and cytochrome P-450 increased significantly in the yeast phase, whereas levels of poly(A) polymerase and SNF22 were reduced.
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PMID:Differentially expressed proteins of pathogenic Penicillium marneffei in yeast and mycelial phases. 1731 57

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes as well as the P-glycoprotein transport system. Several examples of well-documented clinically significant interactions include warfarin, oral contraceptives, cyclosporine, itraconazole, digoxin, verapamil, nifedipine, simvastatin, midazolam, and human immunodeficiency virus-related protease inhibitors. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. Examples of clinically relevant interactions demonstrated by recent reports include everolimus, atorvastatin, rosiglitazone/pioglitazone, celecoxib, clarithromycin, caspofungin, and lorazepam. To avoid a decreased therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Studies and cases of rifampin drug interactions continue to increase rapidly. This review is a timely reminder to clinicians to be vigilant.
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PMID:Update on rifampin and rifabutin drug interactions. 1827 21

Concomitant use of immunosuppressive agents and antiretroviral drugs may lead to complex drug-drug interactions. The calcineurin inhibitor tacrolimus is metabolized by cytochrome P-450 3A4 (encoded by the CYP3A4 gene) and is a substrate of P-glycoprotein (encoded by the ABCB1 gene). Both pathways can be inhibited by protease inhibitors (PIs). The reduction in first-pass and postabsorptive metabolism of tacrolimus by PIs can lead to extreme prolongation of the elimination half-life and significantly increase tacrolimus trough levels. In a patient with human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis leading to kidney cadaveric transplantation, HIV salvage therapy was started with the new PI darunavir and boosted with ritonavir, another PI. The reduction in first-pass and postabsorptive metabolism of tacrolimus by PIs led to a dramatic increase in tacrolimus trough levels and extreme prolongation of the elimination half-life. Trough levels of tacrolimus levels were as high as 106.7 ng/mL. A decrease in tacrolimus dosage to a single dose of 0.5 mg/wk, corresponding to 3.5% of the usual dose, enabled maintenance of stable tacrolimus trough levels. Our case highlights that coadministration of a PI and tacrolimus is feasible through intense reduction in dose and prolongation of the dosing interval of the calcineurin inhibitor. Complex drug interactions may become more frequent because more HIV-infected patients are undergoing transplantation and newer HIV drugs are being used. Close monitoring and excellent adherence are mandatory to avoid the risk of harm for the graft and patient.
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PMID:Drug-drug interaction in a kidney transplant recipient receiving HIV salvage therapy and tacrolimus. 1934 40

Rifabutin-associated uveitis has been recognized as a dosage-dependent side effect. Previous studies have reported that clarithromycin or fluconazole may elevate concentrations of rifabutin through inhibition of metabolism through the cytochrome P-450 pathway. Nelfinavir is a protease inhibitor widely used in the treatment of human immunodeficiency virus (HIV) infection. The interactions between protease inhibitors and rifabutin have not been reported in clinical practice. Therefore, we present a case of bilateral uveitis associated with coadministration of rifabutin and nelfinavir. Uveitis did not subside until discontinuation of rifabutin. To our knowledge, this is the first report of uveitis with concurrent administration of rifabutin and nelfinavir. Our finding reminds us that rifabutin dosage should be reduced when it is administered with protease inhibitors.
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PMID:Bilateral uveitis associated with concurrent administration of rifabutin and nelfinavir. 2901 96


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