Effects of missed dose and delayed dose quetiapine on its pharmacokinetics and pharmacodynamics

Abstract

Nonadherence to the prescribed medication can result in a poor treatment outcome. This study determined the impacts of multiple missed dose or delayed dose scenarios on quetiapine (QTP) pharmacokinetics and pharmacodynamics. QTP concentration-time profiles and Brief Psychiatric Rating Scale (BPRS) scores under multiple missed doses and delayed dose scenarios were simulated using Monte Carlo simulations and compared with those of the full adherence scenario using the Mann-Whitney U test. The simulations were performed using the model structure and parameter estimates obtained from Kimko et al's study. Missing one, two and three consecutive QTP doses significantly decreased trough concentration (Ctrough) by 71.4, 103, and 128ng/mL. However, Ctrough rapidly increased to values close to those of the full adherence scenario when the regular dose was resumed. Further, all missed dose scenarios did not significantly impact the maximum percent reduction of BPRS score from baseline, but significant impacts on the minimum percent reduction of BPRS score from baseline were observed. However, the change in BPRS score from the full adherence scenario rapidly resumed when the regular dose was taken. Moreover, this study identified that a delayed dose as late as 6 hours did not significantly impact the maximum concentrations when the regular dose was resumed. Based on the simulations, a missed dose can be taken as late as 6 hours before the next scheduled dose, otherwise it should be skipped. For multiple missed doses scenarios, QTP pharmacokinetics and pharmacodynamics rapidly returned to the stage close to the full adherence scenario when a single regular dose was resumed.