Abstract 3633: Pharmacokinetic and Hemodynamic Responses to Oral Sildenafil During Invasive Testing in Children With Pulmonary Hypertension
Introduction: Although used frequently for treatment of children with pulmonary arterial hypertension (PAH), data regarding the acute responses to sildenafil are limited. The purpose of our study was to characterize the hemodynamic and corresponding pharmacokinetic responses to a single dose of oral sildenafil in children with PAH undergoing invasive testing.
Patients and methods: 36 patients (mean±SEM, 7.5±0.98 years; 24 female) were studied during cardiac catheterisation with general anesthesia. 8/36 (22%) had idiopathic PAH, the remainder had associated congenital heart disease. Hemodynamics and serum cyclic guanosine-monophosphate levels (cGMP) were evaluated at baseline and after inhaled nitric oxide (NO) (40 ppm). In addition, cGMP and sildenafil levels were measured 30 minutes after administration of sildenafil (0.5 mg/kg, suspended in 5 mls of sterile water) via nasogastric tube.
Results: For the 36 patients the pulmonary vasodilating capability of oral sildenafil was lower than that of inhaled NO (2.8 % versus 11.6 % reduction in pulmonary vascular resistance index (PVRI) respectively, p=0.01). However, only 21/36 (58%) patients had a detectable sildenafil level. In those with detectable sildenafil levels the fall in PVRI was greater (−11.6±5.1 %, p=ns, compared with NO). Mean cGMP levels at baseline and after inhaled NO were 41.8±3.3 and 83.8±5.9 pmol/ml respectively (p<0.0001). Surprisingly there was no significant increase in cGMP in either those with undetectable (37.5±7.7 pmol/ml) or detectable (44.4±6.9 pmol/ml) sildenafil levels (p=ns compared with baseline) with sildenafil.
Conclusions: Our study demonstrates suboptimal absorption of sildenafil in almost half the children undergoing acute hemodynamic testing. When detectable, sildenafil is equipotent to inhaled NO despite lower circulating cGMP levels. These data should be taken into account when designing acute testing protocols, and assessing the acute response to sildenafil in patients with PAH.