Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Bliven-Sizemore EE[original query] |
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Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI
Bliven-Sizemore EE , Sterling TR , Shang N , Benator D , Schwartzman K , Reves R , Drobeniuc J , Bock N , Villarino ME . Int J Tuberc Lung Dis 2015 19 (9) 1039-44 SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred. |
Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers
Dooley KE , Bliven-Sizemore EE , Weiner M , Lu Y , Nuermberger EL , Hubbard WC , Fuchs EJ , Melia MT , Burman WJ , Dorman SE . Clin Pharmacol Ther 2012 91 (5) 881-8 Rifapentine (RPT) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RIF). The maximal tolerated daily dose of RPT and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. In this phase I, dose-escalation study among healthy volunteers, daily doses as high as a prespecified maximum of 20 mg/kg/day were well tolerated. Steady-state RPT concentrations increased with dose from 5 to 15 mg/kg, but area under the plasma concentration-time curve (AUC(0-24)) and maximum concentration (C(max)) were similar in the 15- and 20-mg/kg cohorts. Although RPT pharmacokinetics (PK) appeared to be time-dependent, accumulation occurred with daily dosing. The mean AUC(0-12) of oral midazolam (MDZ), a cytochrome 3A (CYP3A) probe drug, was reduced by 93% with the coadministration of RPT and by 74% with the coadministration of RIF (P < 0.01). Changes in the oral clearance of MDZ did not vary by RPT dose. In conclusion, RPT was tolerated at doses as high as 20 mg/kg/day, its PK were less than dose-proportional, and its CYP3A induction was robust. |
Effect of HIV infection on tolerability and bacteriologic outcomes of tuberculosis treatment
Bliven-Sizemore EE , Johnson JL , Goldberg S , Burman WJ , Villarino ME , Chaisson RE , Tuberculosis Clinical Trials Consortium . Int J Tuberc Lung Dis 2012 16 (4) 473-9 SETTING: Two international, multicenter Phase 2 clinical trials examining fluoroquinolone-containing regimens in adults with smear-positive pulmonary tuberculosis (TB), conducted from July 2003 to March 2007. Both trials enrolled human immunodeficiency virus (HIV) infected participants who were not receiving antiretroviral therapy (ART) at TB treatment initiation. OBJECTIVE: To assess the impact of HIV infection on TB treatment outcomes in Phase 2 clinical trials. DESIGN: Cross-protocol analysis comparing the safety, tolerability and outcomes of anti-tuberculosis treatment by HIV status. RESULTS: Of 750 participants who received at least one dose of study treatment, 123 (16%) were HIV-infected. Treatment completion rates were similar by HIV status (81% infected vs. 85% non-infected), as were rates of week 8 culture conversion (66% infected vs. 63% non-infected), and treatment failure (5% infected vs. 3% non-infected). Among HIV-infected participants, treatment failure detected using liquid media was more frequent in those treated thrice weekly (14% thrice weekly vs. 2% daily, P = 0.03). HIV-infected participants more frequently experienced an adverse event during the intensive phase treatment than non-HIV-infected participants (30% vs. 15%, P < 0.01). CONCLUSION: HIV-infected persons not receiving ART had more adverse events during the intensive phase of anti-tuberculosis treatment, but tolerated treatment well. Failure rates were higher among HIV-infected persons treated with thrice-weekly intensive phase therapy. |
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