Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan
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概要
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The chronic use of bosentan has been reported to reduce the plasma concentration of sildenafil. However, it remains unclear how sildenafil exerts the effect at reduced concentrations in pulmonary arterial hypertension (PAH) patients chronically treated with bosentan.We examined the hemodynamic effects of sildenafil (50 mg) in 8 Japanese patients with PAH, and simultaneously measured the plasma concentration of sildenafil ([Sil]) and its major metabolite, desmethylsildenafil ([Des]).The overall effects of sildenafil were 12.4% decrease in mean pulmonary arterial pressure, 19.9% increase in cardiac index (CI), and 25% reduction in derived pulmonary vascular resistance (PVR). When the patients were divided into two groups, a group with bosentan pretreatment [BOS (+), n = 4] and a group without bosentan pretreatment [BOS (-), n = 4], both [Sil] and [Des] were lower at the peak concentration (Cmax) and the area under the plasma concentration versus time curve (AUC0-6h), and the time to reach Cmax was longer in BOS (+), although only the difference in AUC0-6h of [Des] reached statistical significance (P = 0.02). In spite of lower concentration, the effect of sildenafil on CI was maintained in the BOS (+) group, while the decrease in PVR was less marked.Sildenafil acutely dilated the pulmonary artery and increased CI in the PAH patients. These effects were still observed or maintained in the PAH patients chronically treated with bosentan, even when [Sil] was reduced.
著者
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Hirata Yasunobu
Department Of Advanced Clinical Science And Therapeutics Cardiovascular Medicine Graduate School Of
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Hatano Masaru
Department Of Cardiology Narita Red Cross Hospital
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Kinugawa Koichiro
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
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Yao Atsushi
Department Of Cardiology Tokyo University Hospital
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Nagai Ryozo
Department Cardiovascular Medicine The University Of Tokyo Hospital
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