کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2574740 1129710 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Does rapid dose titration affect the hepatic safety profile of Bosentan?
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Does rapid dose titration affect the hepatic safety profile of Bosentan?
چکیده انگلیسی

RationaleBosentan, a dual endothelin receptor antagonist, has proven efficacy in pulmonary hypertension. Due to an association with hepatic dysfunction, it is typically initiated at a sub-therapeutic dose for 4 weeks before titration to a therapeutic dose. At our institution some patients have undergone rapid titration, to potentially benefit from therapy earlier. This study assesses the impact of this practice on hepatic safety.MethodAll patients initiated on bosentan therapy before April 2005 were included. Rapidly titrated patients achieved a therapeutic dose by 3 days, whereas standard titration patients were titrated at 4 weeks. All patients were monitored with monthly liver function tests.Results149 patients commenced bosentan, of which 55 were rapidly titrated. At baseline, the two groups were similar in age, BMI, diagnosis, 6-min walking distance, alanine aminotransferase (ALT), cardiac index and pulmonary artery pressures. The rapid group had elevated right atrial pressures (9.7 mm Hg versus 7.4 mm Hg, p = 0.016) and worse WHO functional class (p = 0.008) and included less females (31% versus 69%, p = 0.024). The incidence of hepatic dysfunction in all patients was 12.8% at 12 months. There was no statistical difference in incidence between the rapid and standard groups (4% versus 11% at 3 months, p = 0.211 and 6% versus 15% at 12 months, p = 0.219). Of all patients on bosentan, hepatic dysfunction was most significantly associated with a higher baseline ALT (p = 0.021), female sex (p = 0.003) and underlying connective tissue disease (p = 0.025). Subgroup analysis suggested these factors were not confounders when comparing rapid and standard titration.ConclusionsRapid and standard titration of bosentan resulted in similar hepatic safety profiles. Baseline ALT, female sex and the presence of connective tissue disease increased the risk of hepatic dysfunction independent of the titration method used.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vascular Pharmacology - Volume 44, Issue 6, June 2006, Pages 508–512
نویسندگان
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