Simcyp’s Age-Defining Feature Facilitates Everolimus Dosing in Neonates
Everolimus (Afinitor®) was recently approved as adjunctive therapy for tuberous sclerosis complex (TSC)-associated partial seizures in ages 2 and older. Unlike many other therapies for treating TSC-associated seizures, everolimus addresses the underlying pathophysiology of TSC. As TSC-associated seizures can also affect children aged between 6 months and 2 years, a modeling and simulation approach that incorporated Population Pharmacokinetics (PK), Population Pharmacodynamics (PD), and physiologically-based pharmacokinetics (PBPK) was used to extrapolate exposure. The PBPK model, built and qualified in the Simcyp Simulator, predicted everolimus exposure in 200 patients, ages 6 months to 1 year. The PBPK data was incorporated into a Population PD model to simulate the reduction in seizure frequency.