Background: Pulmonary hypertension is a progressive disease of diverse origin with devastating
consequences in children. The phosphodiesterase-5 inhibitor sildenafil successfully
lowers pulmonary vascular resistance. However, responses in infants and children are
often erratic due to poor oral absorption resulting in ineffective plasma concentrations.
In adults, bioavailability (F) of sublingual sildenafil appears considerable suggesting
that this might be a promising alternative route of administration in children with
poor absorption.
Methods: The authors evaluated the plasma concentrations of orally and sublingually administered
sildenafil suspension (4 – 10 mg/d qid) in two children suffering from structural
cardiac and pulmonary defects. Because one child also received sildenafil intravenously,
absolute F could be estimated. Sildenafil and N-desmethyl-sildenafil were measured using a validated LC/MS/MS methodology.
Results: In the first case (6 mo-old boy) sublingual administration resulted in ˜3 times higher
plasma concentrations (12 – 20 vs. 2.7 – 6.9 ng/mL). Exposure of the second child
(2.5-y-old boy) expressed as the area under the curve in the dosing interval (AUC0
– 6h) was 918 (intravenous), 106 (sublingual), and 25 hour ng/mL after oral administration
indicating that estimated oral F increased by 314%. Concurrently in both children
molar metabolic ratios after sublingual sildenafil increased 3- to 8-fold suggesting
a successful bypass of first pass metabolism.
Conclusion: Sublingual sildenafil achieved considerably higher exposure than oral suggesting
that this route of administration might be an attractive way to overcome the frequently
observed poor gastrointestinal absorption and low systemic availability.
