Population Pharmacokinetics and Exposure-Response Relationship of Hemoporfin in Pediatric Patients With Port-Wine Stain.

Hemoporfin, a porphyrin derivative photosensitizer, has been approved for the treatment of port-wine stain (PWS) in adults. However, its optimal dose for the pediatric population remains unclear. This study aimed to explore appropriate dosing for pediatric patients with PWS through population pharmacokinetics (PopPK) and exposure-response (ER) analysis. Data from a prospective pilot study of hemoporfin photodynamic therapy in pediatric PWS patients, as well as a phase I study in healthy adult volunteers, were utilized for the analysis. The pharmacokinetics of hemoporfin in the pediatric population can be described by a three-compartment model with linear elimination following allometric scaling rules. Simulations indicated that simply scaling down the approved adult dose of 5 mg/kg based on weight for the pediatric population, which is a common practice among clinicians, may lead to reduced drug exposure in pediatric patients. Mean Cmax and AUC0-30min in pediatric patients were 18.7% and 30.5% lower than those in adults, respectively. A positive relationship was identified between AUC0-30min and the probability of investigators or patients giving high ratings for efficacy, suggesting that improved efficacy may be achieved with higher hemoporfin exposure. A series of dosing regimens were explored to match exposure in the pediatric population to that of the adult population. These findings may accelerate the development of pediatric indications for hemoporfin and help address the unmet medical needs of pediatric patients with PWS.