Quetiapine serum concentrations in psychiatric patients: the influence of comedication

Steady-state serum concentrations of quetiapine were recorded in 62 psychiatric patients under routine conditions. Doses were administered twice daily, and serum quetiapine levels were measured in the morning about 12 hours after the last dose. Eight patients were in monotherapy, whereas the rest received various additional psychotropic drugs. For the whole group, the concentration-to-dose ratio (C/D) varied 238-fold, with a median value of 0.41 nmol/L/(mg/24 h). For the administered dose range (37.5-1200 mg/24 h), the serum concentrations ranged from below the detection limit (10 nmol/L) to 999 nmol/L. With the exception of 2 subjects receiving carbamazepine and patients receiving quetiapine outside the recommended dose interval, 80% of the rest had serum levels within the range 50 to 650 nmol/L, which may serve as an orienting interval for serum concentrations observed under routine treatment conditions. Patients (n = 38) comedicated with drugs competing for metabolism by CYP3A4 displayed a median C/D value of 0.48 nmol/L/(mg/24 h), which was 70% higher than the C/D value of the monotherapy group [0.28 nmol/L/(mg/24 h)], in contrast to patients receiving drugs metabolized by CYP2D6 with a median C/D of 0.23 nmol/L/(mg/24 h). None of the comedicated groups were significantly different from the monotherapy group. Two subjects comedicated with carbamazepine had very low C/D values [0.02-0.04 nmol/L/(mg/24 h)].