Abstract
Aim A robust and user-friendly software tool was developed for the
prediction of dopamine D2 receptor occupancy (RO) in patients with
schizophrenia treated with either olanzapine or risperidone. This tool
can facilitate clinician exploration of the impact of treatment
strategies on RO using sparse plasma concentration measurements. Methods
Previously developed population pharmacokinetic (PPK) models for
olanzapine and risperidone were combined with a PD model for D2 receptor
occupancy (RO) and implemented in the R programming language. MAP
Bayesian estimation was used to provide predictions of plasma
concentration and receptor occupancy and based on sparse PK
measurements. Results The average (standard deviation) response times of
the tools were 2.8 (3.1) and 5.3 (4.3) seconds for olanzapine and
risperidone, respectively. The mean error (95% confidence interval) and
root mean squared error (RMSE, 95% CI) of predicted versus observed
concentrations were 3.73 ng/mL (-2.42 – 9.87) and 10.816 (6.71 –
14.93) for olanzapine, and 0.46 ng/mL (-4.56 – 5.47) and 6.68 (3.57 –
9.78) for risperidone and its active metabolite (9-OH risperidone). Mean
error and RMSE of RO were -1.47% (-4.65 – 1.69) and 5.80 (3.89 –
7.72) for olanzapine and -0.91% (-7.68 – 5.85) and 8.87 (4.56 –
13.17) for risperidone. Conclusion Treatment of schizophrenia with
antipsychotics offers unique challenges and requires careful monitoring
to establish the optimal dosing regimen. Our monitoring software
predicts RO in a reliable and accurate form.