Detail Strategies to reduce arylamine drug toxicity in people with AIDS Bibliografi Author: Winter, Helen Rayma ; Unadkat, Jashvant D. (Advisor) Topik: HEALTH SCIENCES; PHARMACOLOGY|HEALTH SCIENCES; TOXICOLOGY Bahasa: (EN )    ISBN: 0-599-15604-X     Penerbit: University of Washington     Tahun Terbit: 1998     Jenis: Theses - Dissertation Fulltext: 9916734.pdf (0.0B; 0 download) Abstract The specific aims of this work were to: (1) evaluate the therapeutic strategy of using fluconazole to suppress sulfamethoxazole hydroxylamine formation in HIV-infected patients and provide the basis for future toxicity prevention trials; (2) examine the effect of the commonly co-administered drugs for opportunistic infections, rifabutin (300mg OD), clarithromycin (500mg BD) and fluconazole (200mg OD) on the pharmacokinetics of both dapsone (100mg OD) and sulfamethoxazole (800mg OD) and their respective hydroxylamine production in HIV-infected patients; (3) identify a potentially clinically useful inhibitor of sulfadiazine hydroxylamine production in vitro and (4) determine the inhibitory potential of the protease inhibitors indinavir, nelfinavir, ritonavir and saquinavir on dapsone and sulfamethoxazole hydroxylamine production. Fluconazole was an effective inhibitor of both dapsone and sulfamethoxazole hydroxylamine exposure in HIV-infected patients and suppressed hydroxylamine exposure approximately 50%. Rifabutin increased sulfamethoxazole hydroxylamine exposure by approximately 50% compared to controls, but had no effect on dapsone hydroxylamine exposure. Clarithromycin had no effect on exposure to either dapsone or sulfamethoxazole hydroxylamine. Fluconazole was also found to substantially inhibit sulfadiazine hydroxylamine production in vitro with Ki's ranging from 19–62μM and would be predicted to inhibit hydroxylamine exposure by 40–70% in vivo. Of the protease inhibitors examined only ritonavir has the potential to inhibit sulfamethoxazole and dapsone hydroxylamine production with a Ki for reversible inhibition of 1.44 ± 0.41 μM and IC50 of 1.82 ± 0.35μM, respectively. This work demonstrates the utility of in vitro drug metabolism data to prospectively predict significant drug-drug interactions in vivo. The strategy of using fluconazole to inhibit dapsone and sulfamethoxazole hydroxylamine exposure in HIV-infected patients to decrease rates of adverse reactions should now be examined in much larger toxicity trials. Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Lihat Sejarah Pengadaan  Konversi Metadata   Kembali

Copyright © 2006, 2007 Unika Atma Jaya, all rights reserved