RESUMEN
BACKGROUND: Clozapine is the most effective antipsychotic with respect to the incidence of discontinuation and is indicated for treatment-resistant schizophrenia. Although the recommendation for clozapine administration is divided dosing, once-daily dosing of clozapine is commonly prescribed in many countries. However, there is currently no clinical data comparing all-cause discontinuation between the 2 methods of administration of clozapine. OBJECTIVES: To compare the all-cause discontinuation and safety of clozapine administration between once-daily and divided dosing regimens. METHODS: This was a retrospective cohort study. Participants were patients with treatment-resistant schizophrenia who had received 300 to 600 mg/day of clozapine for at least 3 months. Data were collected from outpatient medical records at Somdet Chaopraya Institute of Psychiatry. Eligible patients were classified into 2 groups: once-daily dosing and divided dosing. The primary outcome was the all-cause discontinuation rate between groups. The duration of the study was 2 years. RESULTS: One hundred eighteen patients were included and analyzed in this study (once-daily dosing group: n = 58; divided dosing group: n = 60). There was no significant difference in all-cause discontinuation between the 2 groups (odds ratio 1.03; 95% confidence interval: [0.28, 3.79]: P = 1.00), or adverse events between groups. CONCLUSION AND RELEVANCE: In patients with treatment-resistant schizophrenia, there were no significant differences in effectiveness or safety between once-daily and divided dosing of clozapine. Further prospective studies with larger sample sizes are required to confirm these findings.
RESUMEN
Busulfan (Bu) is commonly used in myeloablative conditioning regimens for children undergoing hematopoietic stem cell transplantation. The standard target area under the concentration-time curve (AUC) of Bu is approximately 900-1500 µM min. In previous studies using five fixed doses (0.8-1.2 mg/kg) for Bu without dose adjustment, 75% patients achieved the target AUC. The aim of this pilot study was to determine the percentage of target AUC for intravenous (IV) Bu in Thai children. IV Bu was administered every 6 h over 16 doses. Blood samples were collected for pharmacokinetic (PK) analysis after the first, ninth, and thirteenth doses of Bu. Seven patients (2-14 years; median 6 years) were diagnosed with thalassemia (n = 4), acute myeloid leukemia (n = 2), and pure red cell aplasia. Three, two, and two patients received Bu at 1.1, 1.2, and 0.8 mg/kg, respectively. The AUC of Bu varied from 292-1714 µM min (median = 804). Nine (42.86%), eleven (52.38%), and one (4.76%) AUC values were within, below, and above the target, respectively. The median (range) Bu clearance was 5.93 (1.91-14.65) mL/min/kg. In this study, 42.86% AUC value achieved the target, which was lower than that in previous studies. Therapeutic drug monitoring (TDM) of Bu should be considered in Thai children receiving five fixed doses of IV Bu, and dose adjustment should be performed as necessary. Further PK studies for Bu with a larger sample size are warranted for confirming the necessity of TDM in every step dose of Bu.(Trial registration numbers; TCTR20190528003).