Qualification of a select one-stage activated partial thromboplastin time-based clotting assay and two chromogenic assays for the post-administration monitoring of nonacog beta pegol.

Essentials Nonacog beta pegol (N9-GP) is an extended half-life, recombinant human factor IX (FIX). One-stage clotting (OSC) and chromogenic FIX activity assays were assessed for N9-GP recovery. OSC STA® -Cephascreen® , ROX FIX and BIOPHEN FIX chromogenic assays were qualified for N9-GP. Other extended half-life factor products should be assessed in a similar way prior to approval. SUMMARY: Background Nonacog beta pegol (N9-GP) is an extended half-life, glycoPEGylated recombinant human factor IX that is under development for the prophylaxis and treatment of bleeding episodes in hemophilia B patients. Considerable reagent-dependent variability has been observed when one-stage clotting assays are used to measure the recovery of recombinant FIX products, including N9-GP. Objective To qualify select one-stage clotting and chromogenic FIX activity assays for measuring N9-GP recovery. Methods The accuracy and precision of the one-stage clotting assay (with the STA-Cephascreen activated partial thromboplastin [APTT] reagent) and the ROX Factor IX and BIOPHEN Factor IX chromogenic assays for measuring N9-GP recovery were assessed in N9-GP-spiked hemophilia B plasma samples in a systematic manner at three independent sites, with manufacturer-recommended protocols and/or site-specific assay setups, including different instruments. Results For each of the three FIX activity assays qualified on five different reagent-instrument systems, acceptable intra-assay and interassay accuracy and precision, dilution integrity, reagent robustness and freeze-thaw and short-term sample stabilities were demonstrated. The STA-Cephascreen assay showed a limited reportable range at one of the three qualification sites, and the BIOPHEN Factor IX assay showed suspect low-end sensitivity at one of the three qualification sites. An individual laboratory would account for these limitations by adjusting the assay's reportable range; thus, these findings are not considered to impact the respective assay qualifications. Conclusion The one-stage clotting assay with the STA-Cephascreen APTT reagent, the ROX Factor IX chromogenic assay and the BIOPHEN Factor IX chromogenic assay are considered to be qualified for the measurement of N9-GP in 3.2% (0.109 m) citrated human plasma.

Whole saliva and plasma levels of clozapine and desmethylclozapine.

BACKGROUND: Therapeutic drug monitoring of clozapine as an aid in the treatment of schizophrenic states is commonly used in our hospital. OBJECTIVE: Development of a high-performance liquid chromatographic method for the determination of clozapine (CLZ) and its major metabolite desmethylclozapine (DMCLZ) in plasma and saliva, and investigation of the relationship between plasma concentrations of CLZ and DMCLZ and concentrations in saliva in patients treated with clozapine. METHODS: Subjects were either inpatients or outpatients with a DSM IV diagnosis of schizophrenia (n=34). Determination of CLZ and DMCLZ saliva concentrations appeared to be a satisfactory method to check compliance to treatment, particularly in outpatients. RESULTS: Mean CLZ and DMCLZ plasma concentrations were 432+/-264 ng/ml (+/-SD) (range 90-1310 ng/ml) and 257+/-144 ng/ml (range 55-580 ng/ ml), respectively. The CLZ/DMCLZ plasma ratio was equal to 1.7+/-0-5 (daily dosage 7.2+/-2.3 mg/kg, n=34). Mean CLZ plasma and saliva levels were 336+/-157 ng/ ml (range 90-580 ng/ml) and 159+/-86 ng/ml (range 40-364ng/ml), respectively (r=0.56, n=14). Mean DMCLZ plasma and saliva levels were 196+/-112 ng/ ml (range 55-481 ng/ml) and 109+/-67ng/ml (range 40-250ng/ml), respectively (r=0.73, n=14). Mean CLZ/DMCLZ ratios determined in plasma and saliva were 1.9+/-0.6 (range 1.0-3.4) and 1.7+/-0.6 (range 1.0-3.2), respectively (r=0.85, n=14). CLZ and DMCLZ saliva concentrations appear to be useful for checking compliance to treatment, in particular among outpatients.

[4 years using clozapine in community psychiatry]. / Quatre ans d'utilisation de la clozapine en psychiatrie de secteur.

This study report clinical experience of Clozapine treatment in 48 chronic schizophrenic patients. At the study time, 35 patients are still under this treatment while 13 patients have stopped it. These two populations and their differences are presented. Clozapine experience is positive as testifies quality of life and social situation improvement in numerous cases.