Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Itraconazole (R 51211) is the prototype of a class of triazole antifungals characterized by a high lipophilicity. This property determines to a large extent the pharmacokinetics of itraconazole and differentiates it from the hydrophilic triazole antifungal fluconazole. The pharmacokinetics of itraconazole in man are characterized by a good oral absorption, an extensive tissue distribution with tissue concentrations many times higher than in plasma, a relatively long elimination half-life of about one day and a biotransformation into a large number of metabolites. One of them, hydroxy-itraconazole, is antifungally active and explains why antifungal plasma levels, when measured by bioassay, are about three times the itraconazole levels measured by a specific HPLC-method. Distribution studies have shown that therapeutically active levels of itraconazole are maintained much longer in some infected tissues than in plasma. For instance, active levels persist for four days in the vaginal epithelium after a one-day treatment and for 3 weeks in the stratum corneum of the skin after treatment has been stopped. Unlike fluconazole, itraconazole does not interfere with mammalian drug metabolizing enzymes, minimizing the risk of interaction with concomitantly administered drugs. These pharmacokinetic properties may contribute to the high efficacy and safety of itraconazole in patients with various mycotic infections. New pharmaceutical formulations are being explored in order to broaden the application field of itraconazole to intravenous and oral therapy of patients with malabsorption.
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PMID:The clinical pharmacokinetics of itraconazole: an overview. 256 Nov 87

The systematic fungal infections are very serious diseases, the crude mortality in invasive aspergillosis reaches 75 to 100 per cent. Systemic mycosis tends to develop in immunocompromised patients with subsequent physiopathological state, causing a risk of impairment in their digestive absorption potential; in addition these patients are polymedicated and the emergence of multiple drug interactions is frequent. Itraconazole is a very potent antifungal drug with large safety margin and the drug monitoring to maintain a satisfactory plasma level. Immunocompromised patients with suspected malabsorption and treated with oral capsule itraconazole were monitored during two years. In such difficult patients (approximately equal to 500 cases), the result has shown good trough steady-state plasma levels in 72 per cent and insufficient in 28 per cent of the observed patients. However concomitant treatments with antacids produce, in a lot of cases (approximately equal to 48 per cent), a noticeable decrease of the itraconazole availability for these patients. A training program was established to perform the analytical determination of itraconazole and hydroxyitraconazole in biological samples by HPLC method. Analytical validation procedures were associated to this training program which included 115 scientific, technical staff (pharmacists, biochemists ...) from 56 hospitals and institutes.
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PMID:[Example of active therapeutic follow-up: itraconazole]. 913 84