Therapeutic Drug Monitoring of Lurasidone in Patients with Schizophrenia or Bipolar Disorder: A preliminary study

Abstract

Lurasidone is a second-generation antipsychotic agent indicated for schizophrenia and bipolar depression. Lurasidone is metabolized mainly by cytochrome P450 (CYP) 3A4, and drug-drug interaction needs to be considered. 1 Plasma concentrations (Cps) in 44 clinically stable patients (mean age, 47.8 AE 12.9 years, body weight [BW] 71.4 AE 14.8 kg) taking lurasidone for at least 1 month with informed consent were monitored after dosing for around 15 hours. Table 1 presents the mean Cps, Cps/daily dose (DD), and Cps/DD/BW among the patients and the breakdown by sex. Pearson correlation coefficient for Cps and DD/BW was 0.036, suggesting a wide interindividual range. Many factors contribute to this variation, such as genetic differences in the first-pass effect of the CYP system, sex, medication adherence, dosing time, and whether the medication is taken with meals. Because CYP3A4 plays a major role in the metabolism of lurasidone, this system exhibits remarkable interindividual activity variation as high as 20-fold 2 and racial genetic differences. 3 These differences may account for some of the Cps variations in the results.As most patients were in stable clinical condition, we assumed that their prescribed lurasidone dosage was suitable. Considering that the elimination half-life of lurasidone is approximately 18 hours, 4 and that our results were from approximately 15 hours after dosing, the trough mean Cps should be adjusted by 85% to 13.0 ng/mL and the median to 10.9 ng/mL. Using our preliminary results, we suggest that the therapeutic range of lurasidone in the maintenance phase be 10 to 15 ng/mL, which is slightly lower than the suggested range of 15 to 40 ng/mL by Hiemke et al. 5 In a study of 38 healthy Chinese men administered a 40-mg dose of lurasidone, 6 the area under the curve was 37% higher in Chinese than in Western participants. Findling et al. 7 conducted a pharmacokinetic study of lurasidone in children and adolescents and found it was similar to exposure observed at a steady state in adults. In the group receiving 80 mg/day, the 15 h Cps was approximately 9.5 ng/mL by extrapolation, which is approximately 40% lower than our results (15.7 AE 12.8 ng/mL, n = 35). From these two independent results, we infer that Chinese individuals might have a 30% to 40% higher Abbreviations: BW, body weight; Cps, plasma concentrations; DD, daily dose.

Racial/Ethnic Differences in the Pharmacokinetics of Antipsychotics: Focusing on East Asians

“…They presented the mean steady state Cps of lurasidone in the group receiving 80 mg/day. The 16-h Cps was approximately 9.5 ng/mL by extrapolation, which was approximately 40% lower than those reported by our findings [70] (15.7 ± 12.8 ng/mL, n = 35).…”

“…Lurasidone is mainly metabolized by CYP3A4 [69]. Our group measured the Cps of lurasidone in 44 patients, with a mean dose of 82.7 ± 23.5 mg/day [70]. The mean plasma concentration 14-16 h after dosing was 15.3 ± 12.5 ng/mL, and the Cps/DD was 0.199 ± 0.188 ng/mL/mg.…”

Post‐therapy plasma concentrations of quetiapine in Taiwanese patients

“…Higher Cps in Oriental patients have also been reported for clozapine, a substrate of CYP 1A2 and 2C19, 10,35 aripiprazole, a substrate of CYP2D6 and 3A4, 36 and lurasidone, a substrate of CYP 3A4 37 . These differences have been observed among different racial populations.…”