The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring.

Several factors can influence s-clozapine and thereby the occurence of dose-related adverse reactions and level of treatment response. The role of Therapeutic Drug Monitoring (TDM) in clozapine dose adjustment have been debated. Blood samples for s-clozapine monitoring are recommended to be drawn 12 hours post dose. Uncertainty regarding the timing of blood sampling and the individual pharmakokinetics for clozapine +/- 2 hours from the 12-hour timepoint, leads to uncertainty regarding the comparability of serum concentrations and the information hold within them.

The scope of this trial is to describe changes of s-clozapine and s-N-desmethyl-clozapine within the range of 10-14 hours after the last administration of clozapine .

In addition we want to investigate if any of the following covariates might affect the change of s-clozapine and s-N-desmethyl-clozapine: Sex, age, BMI, co-medications, signs of infection, caffeine intake and smoking.

Inclusion criteria

• Age 18 < 65
• Diagnosed with schizophrenia according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
• Unchanged dose of clozapine for the last 30 days
• Usual time of clozapine evening-dose administration between 9 and 12 pm.

Exclusion criteria

• Significant drug or alcohol abuse that affects participation in this trial
• Non- or partial compliance of clozapine the day before the trial (assessed by interview)
• Unresponsive by telephone the evening before the trial
• Consumption of clozapine in the morning on the day of the trial
• Significant change in smoking habits within the last 30 days (assessed by interview)
• Significant change of caffeine intake within the last 7 days (assessed by interview)
• Modified use of other antipsychotics within the last 30 days
• Within the last 30 days (7 days for hormone based contraceptives) changes in the use of other medications that can affect s- clozapine during the trial : ( fluvoxamine, ciprofloxacin, hormone based contraceptives, carbamazepine , phenytoin , rifampicin, omeprazole )
• Females who are pregnant or breast-feeding