Prediction of Corresponding Dose of Transdermal Blonanserin to Oral Dose Based on Dopamine D2 Receptor Occupancy

Abstract

Background/Purpose Blonanserin is an atypical antipsychotic, a potent selective antagonist of dopamine D 2 receptor (D 2 ), prescribed as oral formulations in patients with schizophrenia. Blonanserin transdermal patch was developed to provide a new treatment option, but the corresponding dose to oral blonanserin was not clear. The aims of this study were to clarify the pharmacokinetic (PK)-pharmacodynamic characteristics of blonanserin after transdermal patch application and to evaluate the corresponding dose to oral formulation based on striatal D 2 occupancy. Methods The relationship between D 2 occupancy and plasma blonanserin concentration was analyzed using an E max model based on data from positron emission tomography study with oral and transdermal blonanserin. D 2 occupancy was simulated using E max models based on the observed plasma concentrations and the simulated plasma concentrations obtained from population PK model. Results Plasma blonanserin concentration levels after repeated patch applications were nearly stable throughout the day and no effect of sex, advanced age, or application site was detected. The concentration at half maximal D 2 occupancy during transdermal patch applications, 0.857 ng/mL, was higher than that after oral doses, 0.112 ng/mL, suggesting metabolite contribution after oral doses. The median predicted D 2 occupancy during blonanserin patch applications at doses of 40 and 80 mg/d was 48.7% and 62.5%, respectively, and the distribution of D 2 occupancy at these doses could cover most of that at oral doses of 8 to 24 mg/d. Conclusions Predicted D 2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.