Relationship Between Clinical Efficacy and Clozapine Concentrations in Plasma in Schizophrenia

Plasma Clozapine and Desmethylclozapine Levels in Clozapine-Induced Agranulocytosis

“…Plasma clozapine and desmethylclozapine level for the fIve subjects (two females, three females) who devel oped agranulocytosis are given in (Hasegawa et al 1993). The clozapine and desmethylclozapine lev els in the two groups were not signifIcantly different.…”

“…These samples were obtained approximately 12 hours to 16 hours after the evening dose. The plasma concentrations of clozapine and desmethylclozapine was determined in duplicate by high pressure liquid chromatography in diff erent as says (Hasegawa et al 1993). The coefficient of variation was � 6.8% (clozapine), and 6.7% (desmethylclozapine) within assays, � 9.5% (clozapine) and 14.4% (des methylclozapine) between assays.…”

Evaluation of N-Desmethylclozapine as a Potential Antipsychotic—Preclinical Studies

“…In a recent study by Weiner et al (2004) showed that higher NDMC/clozapine ratios predicted greater improvement in subscales of quality of life measures, multiple measures of cognition as well as in some subscales of negative symptomatology and also predicted improvement in delusions, but not hallucinations. However, not everyone finds a positive impact of higher NDMC/ clozapineFeven this measure has met with conflicting findings in terms of clinical response to clozapine treatment ranging from no correlation (Dettling et al, 2000;Mauri et al, 2004) to a positive one (Hasegawa et al, 1993;Spina et al, 2000;Frazier et al, 2003;Mauri et al, 2003;Weiner et al, 2004). Thus, while one can only draw indirect inferences from mixed NDMC/clozapine studies, there are some hints that NDMC may be contributing additional anti 'psychotic' or pro-cognitive efficacy via its muscarinic effects.…”

Effects of Clozapine on In Vitro Immune Parameters A Longitudinal Study in Clozapine-Treated Schizophrenic Patients

“…This is in line with the results of Sperner-Unterweger and colleagues (1993), who reported that a clozapine in vitro concentration of 30 g/ ml led already to a more than 50% reduction in the proliferative response of PBMC in both clozapine-treated patients and untreated healthy controls. However, as serum concentrations achieved during clozapine treatment range from 0 to 1.0 g/ml (Hasegawa et al 1993(Hasegawa et al , 1994, these toxic in vitro effects of clozapine are probably without clinical relevance.…”

“…Thus, SpernerUnterweger and colleagues (1993) may have missed this critical time period in their cross-sectional study, in which they found no effect of clozapine in vitro concentrations of 7.5 g/ml and higher. Although the relationship between clozapine plasma and in vitro concentrations for PBMC is unknown, it is striking that the range of clozapine in vitro concentrations that significantly affected stimulation indices during the first 2 weeks is in the range of clozapine plasma levels reached in vivo (Hasegawa et al 1993;Ackenheil 1989).…”