Prediction of Corresponding Dose of Transdermal Blonanserin to Oral Dose Based on Dopamine D2 Receptor Occupancy: Unique Characteristics of Blonanserin Transdermal Patch.

Background/purpose: Blonanserin is an atypical antipsychotic, a potent selective antagonist of dopamine D2 receptor (D2), prescribed as oral formulations in patients with schizophrenia. Blonanserin transdermal patch was developed to provide a new treatment option, but the corresponding dose to oral blonanserin was not clear. The aims of this study were to clarify the pharmacokinetic (PK)-pharmacodynamic characteristics of blonanserin after transdermal patch application and to evaluate the corresponding dose to oral formulation based on striatal D2 occupancy.

Imeglimin population pharmacokinetics and dose adjustment predictions for renal impairment in Japanese and Western patients with type 2 diabetes.

Imeglimin is an orally administered first-in-class drug to treat type 2 diabetes mellitus (T2DM) and is mainly excreted unchanged by the kidneys. The present study aimed to define the pharmacokinetic (PK) characteristics of imeglimin using population PK analysis and to determine the optimal dosing regimen for Japanese patients with T2DM and chronic kidney disease (CKD). Imeglimin plasma concentrations in Japanese and Western healthy volunteers, and patients with T2DM, including patients with mild to severe CKD with an estimated glomerular filtration rate (eGFR) greater than 14 ml/min/1.

Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D Receptor Occupancy in Clinical Settings.

Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D and D and serotonin 5-HT receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings.

Prediction methods of drug-drug interactions of non-oral CYP3A4 substrates based on clinical interaction data after oral administrations - Validation with midazolam, alfentanil, and verapamil after intravenous administration and prediction for blonanserin transdermal patch.

Drug-drug interactions (DDI) have been examined for various drugs for oral use, but less for non-oral applications. This study provides DDI prediction methods for non-orally administered CYP3A4 substrates based on clinical DDI data of oral dosages. Gut availability (F) and fraction contribution of CYP3A4 to hepatic intrinsic clearance (fm) were predicted by AUC ratio (AUCR) in oral DDI study with/without grapefruit juice, and alteration in intrinsic clearances with/without ketoconazole, respectively.

Cerebrospinal pharmacokinetic and pharmacodynamic analysis of efficacy of meropenem in paediatric patients with bacterial meningitis.

Background: Meropenem is widely used for the treatment of paediatric patients with bacterial meningitis, but the pharmacodynamic (PD) basis for this has not been fully elucidated.

Objectives: A cerebrospinal pharmacokinetic (PK) and PD analysis was performed to identify the optimal dosage regimen for paediatric patients with inflamed central nervous system disease (bacterial men-ingitis).

Patients And Methods: Paediatric data from three clinical studies were used to build a novel population PK model with a cerebrospinal fluid (CSF) compartment, assuming CSF clearance of 0.

Pharmacokinetic evaluation of liposomal amphotericin B (L-AMB) in patients with invasive fungal infection: Population approach in Japanese pediatrics.

Unlabelled: The pharmacokinetic characteristics of liposomal amphotericin B (L-AMB; AmBisome(®)) in patients with invasive fungal infection were investigated. A population pharmacokinetic (PK) model in Japanese pediatric patients was developed based on 159 serum amphotericin B (AMPH-B) concentrations obtained in a post-marketing clinical study. The subjects were 39 patients with a mean age of 8.

Optimal treatment schedule of meropenem for adult patients with febrile neutropenia based on pharmacokinetic-pharmacodynamic analysis.

The objectives of this study were to develop a population pharmacokinetic (PK) model of meropenem, to simulate the percent time above minimum inhibitory concentration (%T > MIC) at various MICs, and to estimate effective dosage regimens by calculating the target attainment rates against various strains of bacteria. A total of 209 plasma samples (1-3 concentrations per patient) were obtained from 98 adult Japanese patients with febrile neutropenia in an open-labeled Phase 3 study. The final population PK model was fit to a two-compartment model with zero-order input.

Optimal dosage regimen of meropenem for pediatric patients based on pharmacokinetic/pharmacodynamic considerations.

A population pharmacokinetic (PK) model for meropenem in Japanese pediatric patients with various infectious diseases was developed based on 116 plasma concentrations from 50 pediatric patients. The population PK parameters developed in this analysis are useful for calculation of the percent time above minimum inhibitory concentration (%T>MIC) and for optimal dosing of meropenem in pediatric patients. After dosing at 20 mg/kg t.

Pharmacokinetics of beclomethasone dipropionate in an hydrofluoroalkane-134a propellant system in Japanese children with bronchial asthma.

Background: Hydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma.

Methods: Plasma concentrations of beclomethasone 17-monopropionate (17-BMP),a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 microg as four inhalations from 50 microg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters.