Changes in psychopharmacotherapy for patients with schizophrenia in a psychiatric institution in Japan: A 12-year prescription survey pre- and post-introduction of clozapine.

Psychopharmacotherapy for patients with schizophrenia in Japan has a long history of polypharmacy, which is rare worldwide but remains a critical problem. One reason for this is that clozapine was not available in Japan until 2009. We aimed to investigate the changes in psychopharmacotherapy in patients with schizophrenia over 12 years pre- and post-introduction of clozapine to clarify how psychopharmacotherapy for patients with schizophrenia has changed with the introduction of clozapine. We retrospectively collected data from the medical records of inpatients diagnosed with schizophrenia at the Okayama Psychiatric Medical Center. Chlorpromazine equivalent (CP-eq) decreased from 1276.6 mg/day in 2009 to 613.9 mg/day in 2020. The prescribed daily dose/defined daily dose (PDD/DDD) decreased from 3.0 in 2009 to 1.2 in 2020. The monotherapy rate increased from 24.4 % in 2009 to 74.6 % in 2020. Our institution began using clozapine in 2010, and the prescription rate for clozapine increased to 37.3 % in 2020. The prescription rate for more than three antipsychotics decreased from 27.8 % in 2009 to 0.8 % in 2020. The increase in clozapine prescription has contributed to an increased rate of antipsychotic monotherapy and a decreased rate of polypharmacy, promoting the optimization of schizophrenia medication. Clozapine therapy should be further promoted in Japan to reduce treatment-resistant schizophrenia due to polypharmacy as much as possible.

Rapid, simple, and clinically applicable high-performance liquid chromatography method for clinical determination of plasma colistin concentrations.

BACKGROUND: Since both the antibacterial effects and common adverse effects of colistin are concentration-dependent, determination of the most appropriate dosage regimen and administration method for colistin therapy is essential to ensure its efficacy and safety. We aimed to establish a rapid and simple high-performance liquid chromatography (HPLC)-based system for the clinical determination of colistin serum concentrations. METHODS: Extraction using a solid-phase C18 cartridge, derivatisation with 9-fluorenylmethyl chloroformate, and elution with a short reversed-phase Cl8 column effectively separated colistin from an internal standard. The HPLC apparatus and conditions were as follows: analytical column, Hydrosphere C18; sample injection volume, 50 µL; column temperature, 40 °C; detector, Shimadzu RF-5300 fluorescence spectrophotometer (excitation wavelength, 260 nm; emission wavelength, 315 nm); mobile phase, acetonitrile/tetrahydrofuran/distilled water (50,14,20, v/v/v); flow-rate, 1.6 mL/min. RESULTS: The calibration curves obtained for colistin were linear in the concentration range of 0.10-8.0 µg/mL. The regression equation was y = 0.6496× - 0.0141 (r2 = 0.9999). The limit of detection was ~ 0.025 µg/mL, and the assay intra- and inter-day precisions were 0.87-3.74% and 1.97-6.17%, respectively. The analytical peaks of colistin A, colistin B, and the internal standard were resolved with adequate peak symmetries, and their retention times were approximately 8.2, 6.8, and 5.4 min, respectively. Furthermore, the assay was successfully applied to quantify the plasma colistin levels of a haemodialysis patient. CONCLUSION: The assay is a simple, rapid, accurate, selective, clinically applicable HPLC-based method for the quantification of colistin in human plasma.

A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia.

Myelosuppression is major treatment-related adverse events of linezolid therapy and result in treatment termination in some cases. We aimed to identify the risk factors for linezolid-induced thrombocytopenia and anemia. We retrospectively retrieved demographic and laboratory data from the medical records of 221 Japanese patients who were undergoing linezolid therapy. Thrombocytopenia and anemia were defined as an unexplained reduction of >30% in the patient's platelet count and hemoglobin level, respectively, from the baseline. Thrombocytopenia developed in 48.4% of patients, and anemia developed in 10.4% of patients during linezolid therapy. In multivariate analysis, creatinine clearance (adjusted odds ratio = 0.94 [0.92-0.95], P < 0.001), hemodialysis (3.32 [1.14-9.67], P = 0.011), and the duration of linezolid therapy (1.14 [1.07-1.21], P < 0.001) were found to be significant risk factors for linezolid-induced thrombocytopenia. Patients with creatinine clearance rates of <60 mL/min and those on hemodialysis were found to be at high risk of linezolid-induced thrombocytopenia. In addition, a high incidence of linezolid-induced thrombocytopenia was even detected among the patients that had received linezolid therapy for <7 days. As for anemia, the duration of linezolid therapy (1.04 [1.01-1.07], P = 0.011) was shown to be a risk factor for anemia, and a high incidence of anemia was seen among the patients who received linezolid for >15 days. In conclusion, we recommend that among patients receiving linezolid therapy the platelet counts of those with risk factors for linezolid-induced thrombocytopenia should be monitored closely throughout treatment, and the hemoglobin levels of patients that receive linezolid for >15 days should be carefully monitored on a weekly basis to detect anemia.

Effects of the fluoroquinolone antibacterial drug ciprofloxacin on ventricular repolarization in the halothane-anesthetized Guinea pig.

The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K(+) channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6). The extents of its effects on the ventricular repolarization phase were comparable to those of another fluoroquinolone antibiotic moxifloxacin at a clinically relevant dose of 3 mg/kg (n = 6). Meanwhile, the PR interval and QRS width were also increased by ciprofloxacin at 10 mg/kg, suggesting that the drug inhibited cardiac K(+) channels as well as Na(+) and Ca(2+) channels in vivo. These results suggest that ciprofloxacin exerted a multi-ion channel-blocking action in the heart within the supra-therapeutic dose range. Therefore, careful observation may be necessary for patients with heart disease receiving a higher dose of ciprofloxacin in order to prevent the emergence of resistance.

Investigation of the clinical efficacy and dosage of intravenous ciprofloxacin in patients with respiratory infection.

PURPOSE: Infection control is particularly vital in hospitals, and proper use of antimicrobial drugs is one of the most important roles of hospital pharmacists. In this study, we surveyed patients who had been prescribed single-use ciprofloxacin (CPFX), and evaluated the blood concentration of CPFX from the predictive AUC (area under the concentration curve). METHODS: This study was performed retrospectively to 112 adult patients diagnosed as having respiratory infections who had been treated as inpatients with intravenous CPFX for more than 3 days at Toho University Omori Hospital in Tokyo. The predictive AUC of each patient was obtained from the modified formulae reported by Forrest et al. (1993) [1]. The relation between the antimicrobial activity of CPFX and pharmacokinetic/pharmacodynamic (Cmax, AUC and AUC/MIC (minimum inhibitory concentration)) was studied. RESULTS: Although CPFX is excreted from the kidney, standard treatment with this drug does not take renal function into consideration. Our results indicated that CPFX was effective in less than 50% of the patients who received it. Moreover, the AUC/MIC ratio in both the effective group and the failure group was less than 125 when the clinical target was gram-negative bacteria. CONCLUSION: These results suggest that the clinical use of CPFX for the treatment of infectious diseases does not reach the target AUC/MIC ratio, and that the concentration of CPFX is not within the range to which many pathogens are susceptible in a large proportion of patients. To ensure the effective treatment of patients with infectious diseases and to prevent the development of resistance in bacteria, we recommend therapeutic drug monitoring (TDM) of CPFX in hospitals.

[Case of serious renal failure induced by ingesting large volume of MAKIRON].

A 23-year-old male patient ingested 150 mL of MAKIRON in a suicide attempt and was transferred to the hospital emergency room approximately 30 hours after ingestion. Upon admission, components of MAKIRON, including naphazoline (1.4 microg/mL), chlorpheniramine (0.81 microg/mL), dibucaine (3.2 microg/mL) and benzethonium (5.5 microg/mL) were detected in the patient's plasma. Direct hemoperfusion and hemodiafiltration enforcement were carried out and the chemical components of MAKIRON were not detected the following day. At the time of hospitalization, the patient presented with serious hepatopathy, pneumonia and acute renal failure. The hepatopathy and pneumonia resolved several days later; however, the patient required continuation of dialysis three times per week for seventeen days due to persistence of anuria. Few case reports on renal failure induced by MAKIRON have been published, whereas there are occasional reports of MAKIRON poisoning. Serious renal dysfunction in this case is thought to be due to both the large volume of MAKIRON ingested and the time delay between ingestion and treatment.