Relation of Blood Counts during Clozapine Treatment to Serum Concentrations of Clozapine and Nor-Clozapine

Abstract

Ob jec tive: To de ter mine the re la tion be tween se rum clo zap ine and nor-clozapine lev els and blood cell counts dur ing clo zap ine treat ment. Method:We un der took a pro spec tive lon gi tu di nal study of 37 con secu tive pa tients with a di ag no sis of schizo phre nia treated with clo zap ine. We ob tained in formed con sent and then de ter mined se rum con cen tra tions of clo zap ine and nor-clozapine weekly. Clo zap ine was ad min is tered daily in di vided doses given every 12 hours and ad justed ac cord ing to clini cal guide lines for its use. Sam ples for se rum con cen tra tions were taken at steady state, im medi ately be fore the next morn ing's dose, for 4 to 8 weeks. Com plete blood counts (CBC), weight, and vi tal signs (that is, blood pres sure, pulse, and tem pera ture) were also moni tored weekly be fore the morn ing's dose of clo zap ine was ad min is tered.Re sults: Analy ses of vari ance showed no sig nifi cant changes over the 8-week treat ment course in the ob served mean white blood count (WBC), red blood count (RBC), neu trophils, and lym pho cytes counts, or in the he mo glo bin and he ma to crit. Only a few weak corre la tions (r < 0.21) were found be tween these he ma to logi cal pa rame ters and the meas ures of se rum clo zap ine and nor-clozapine. Con clu sions:The mecha nism of clozapine-induced he ma to tox ic ity at the thera peu tic dosage range is proba bly not by di rect tox ic ity of clo zap ine or nor-clozapine to the blood cells or their pre cur sors. The for ma tion of the cy to toxic nitrenium com pound from clo zap ine by neu tro phils may be nec es sary. Clini cal Im pli ca tions• The white blood count (WBC), red blood count (RBC), neu tro phils, and lym pho cytes counts show no sig nifi cant changes within 8 weeks of clo zap ine treat ment at thera peu tic dosages.• There is no re mark able cor re la tion be tween blood counts and se rum clo zap ine and norclozapine lev els.• The clo zap ine dos age is sig nifi cantly and highly cor re lated with lev els of se rum clo zap i ne and nor-clozapine, but not with the se rum nor-clozapine-clozapine ra tio. Limi ta tions• The sam ple size was mod er ate.• Only data from the first 8 weeks of treat ment were in cluded.• Cross-cultural rep li ca bil ity is un known.

Clozapine and desmethylclozapine: correlation with neutrophils and leucocytes counting in Mexican patients with schizophrenia

“…They found a positive correlation between neutrophils count and plasma DMC concentrations. Other authors have found no correlation between plasma CLZ and cells‘counting [23, 24]. Two factors may explain the differences between the results presented here and previous studies exploring the subject: 1) Methodological differences, as some studies are case reports of patients with agranulocytosis or longitudinal short-term studies 2) Obvious differences in populations’ genetics and a higher percentage of smokers in the study by Smith et al may account for the different results obtained.…”

Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine

“…Our study did not reveal any signifi cant relationship between the platelet count and serum concentrations of CBZ, CBZE or MHCBZ, suggesting that CBZ or OXCBZ-induced thrombocytopenia is not mediated by direct toxicity of these drugs or its metabolites on the circulating platelets. Similar results have been described for hematotoxicity induced by other drugs such as clozapine 19 . However, in the epileptic patients studied, a weak but signifi cant negative correlation was obtained between the platelet count and the daily doses of CBZ and OXCBZ.…”

Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N‐desmethyl Clozapine (Norclozapine) in human serum

“…Were it not for its side effects, Clozapine would be the first-line treatment; however the rare but potentially lethal side effects of agranulocytosis and myocarditis relegate it to third-line use. Clozapineinduced hematotoxicity at the therapeutic dose range is not directly related to plasma concentrations of Clozapine or Norclozapine (35). Plasma levels of Clozapine do correlate with EEG changes and are thereby a good indicator of electrophysiological reactions to the drug (36,37).…”