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Long-term pharmacokinetics of clozapine
1Department of Biological Psychiatry, Innsbruck University Clinics, Austria.
Background:
Previous studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine.
Method:
Forty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation.
Results:
Dose-plasma level correlations stayed significant from Week 6 to Week 26 (n = 41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically.
Conclusions:
Even though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.