Safety, tolerability and pharmacokinetics of an intravenous bolus of sildenafil in patients with pulmonary arterial hypertension

Abstract

Aims: To assess pharmacokinetics and pharmacodynamics of a 10 mg intravenous sildenafil bolus in pulmonary arterial hypertension (PAH) patients stabilized on 20 mg sildenafil orally three times daily.

Methods: Pharmacokinetic parameters were calculated using noncompartmental analysis.

Results: After an acute increase, plasma concentrations stabilized within the range reported previously for a 20 mg oral tablet. At 0.5 h, mean ± SD changes from baseline were -8.4 ± 11.7 mmHg (systolic pressure), -2.6 ± 7.3 mmHg (diastolic pressure) and -3.5 ± 10.4 beats min(-1) (heart rate). There was no symptomatic hypotension.

Conclusions: Although further research is warranted, a 10 mg sildenafil intravenous bolus appears to provide similar exposure, tolerability and safety to the 20 mg tablet.

Trial registration: ClinicalTrials.gov NCT00800592.

© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Figures

Figure 1

In 10 patients with pulmonary arterial hypertension (PAH) who were stabilized on 20 mg oral sildenafil three times daily and had their morning oral sildenafil dose replaced with a 10 mg bolus intravenous sildenafil dose, individual sildenafil plasma concentrations after the bolus dose are shown (continuous lines). These are superimposed on plasma concentrations associated with oral sildenafil 20 mg three times daily dosing in a population pharmacokinetic model established using the data from 206 patients with PAH in a multinational, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of oral sildenafil (20, 40 or 80 mg three times daily) over a 12 week period: 95% range of the individual predicted concentrations (hatched area) and the mean concentration time profile (bold dashed black line) [6, 7].