Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide. An adrenocorticotrophic hormone (ACTH) test (250 microg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls. Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2-10 months after itraconazole treatment had been discontinued. Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.
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PMID:Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide. 1216 60

In a randomized crossover study, 11 healthy volunteers took 100 mg (first dose 200 mg) of the antifungal drug itraconazole, a P-glycoprotein and CYP3A4 inhibitor, or placebo twice daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren, a renin inhibitor used in the treatment of hypertension. Itraconazole raised the peak plasma aliskiren concentration 5.8-fold (range, 1.1- to 24.3-fold; P < .001) and the area under the plasma aliskiren concentration-time curve 6.5-fold (range, 2.6- to 20.5-fold; P < .001) but had no significant effect on aliskiren elimination half-life. Itraconazole increased the amount of aliskiren excreted into the urine during 12 hours 8.0-fold (P < .001) and its renal clearance 1.2-fold (P = .042). Plasma renin activity 24 hours after aliskiren intake was 68% lower during the itraconazole phase than during the placebo phase (P = .011). In conclusion, itraconazole markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren. The interaction is probably mainly explained by inhibition of the P-glycoprotein-mediated efflux of aliskiren in the small intestine, with a minor contribution from inhibition of CYP3A4. Concomitant use of aliskiren and itraconazole is best avoided.
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PMID:Itraconazole, a P-glycoprotein and CYP3A4 inhibitor, markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren. 2040 Jun 51

Itraconazole is a triazole agent used in the treatment of fungal infections and in some metastatic cancers. Its use has been associated with cardiovascular adverse events and particularly heart failure with preserved ejection fraction. We report the case of a 68-year-old male patient with a well-controlled hypertension treated with irbesartan 150mg/day since 2007. He developed a pulmonary aspergillosis on post-tuberculosis cavitary lesions treated in July 2011 with itraconazole 200mg/day. Early 2012, his antihypertensive treatment had to be gradually increased to a quadritherapy and his blood pressure was at 157/78mmHg at home. Hypokalemia was observed on several occasions as well as edema of the lower limbs. Plasma renin and plasma and urine aldosterone concentrations on treatment not interfering with the renin angiotensin system were low, associated with normal serum and urine cortisol, ACTH, SDHA and DOC, BNP and creatinine concentrations. Plasma itraconazole values were much above the therapeutic range. Left ventricular ejection fraction was preserved. There were no adrenal or renal artery abnormalities at the CT scan. Three months after stopping itraconazole, hypokalemia and edema disappeared and blood pressure was normalized with less treatment. Plasma renin and aldosterone concentrations were normalized. He had a pulmonary lobectomy for his pulmonary aspergillosis. Itraconazole may induce a resistant hypertension with low renin. The mechanisms of this adverse effect of itraconazole remain unknown.
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PMID:[Itraconazole: a new drug-related cause of hypertension]. 2495 75