Tadalafil may fulfill unmet need in pediatric patients with PAH
The first population pharmacokinetic model for tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) demonstrated that plasma tadalafil concentrations were similar in patients aged 2 to <18 years to adults at similar doses, according to a study
Pharmacokinetic data from two phase 3 trials (H6D-MC-LVIG an open-label, multicenter, multiple ascending dose study in pediatric patients with PAH and PHIRST-1, a multicenter, randomized, double-blind, placebo-controlled, parallel design study in adults with PAH who received tadalafil at either 2.5, 10, 20, or 40 mg, or placebo orally, once daily) were pooled to develop a pediatric population PK model for tadalafil. Overall, 1430 observations from 305 adult patients from PHIRST and 19 pediatric patients were analyzed.
According to the study, area under the concentration-time curves (AUCs) for the doses studied were within the range of those associated with improved exercise ability in adults with PAH. Plasma tadalafil concentrations were similar in pediatric patients aged 2 to <18 years and adults at similar doses.
The researchers concluded that in pediatric patients ≥2 years, 40 mg once daily with a bodyweight ≥40 kg and 20 mg once daily with a bodyweight <40 kg undergo phase 3 evaluation.
Ferguson-Sells L, Velez de Mendizabal N, Li B, Small D. Population Pharmacokinetics of Tadalafil in Pediatric Patients with Pulmonary Arterial Hypertension: A Combined Adult/Pediatric Model. Clin Pharmacokinet. 2021;doi: 10.1007/s40262-021-01052-8. Epub ahead of print. PMID: 34379314.