Kosuke Doki

AIM: To assess whether or not co-administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high-dose MTX (HDMTX) therapy for malignant diseases.

METHODS: To assess the effects of PPI co-administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co-administration as a risk ...

AIMS: The aim of this study was to clarify the effects of CYP2D6 genotype on age-related change in flecainide metabolism in patients with supraventricular tachyarrhythmias. An in vitro study using microsomes was performed to identify other CYPs responsible for age-related change in flecainide metabolism.

METHODS: The study population comprised 111 genotyped patients: CYP2D6-homozygous extensive metabolizers (hom-EMs, n= 34), heterozygous EMs (het-EMs, n= 56), and intermediate and poor ...

ObjectiveTo examine the effect of CYP2D6 genotype on the pharmacokinetics of flecainide, we conducted a population pharmacokinetic analysis of the data collected during routine therapeutic drug monitoring of Japanese patients with supraventricular tachyarrhythmia.MethodsPopulation analysis was performed on retrospective data from 58 patients with normal kidney and liver function treated with oral flecainide for supraventricular tachyarrhythmia. Serum concentrations of flecainide were ...

BACKGROUND: Erlotinib is used for treating non-small cell lung cancer (NSCLC). Intestinal absorption of erlotinib is impaired under gastric pH elevation; therefore, coadministration of gastric acid suppressants may provide lower blood concentration of erlotinib. We investigated the effects of erlotinib coadministration with proton pump inhibitors (PPIs) and histamine H2 receptor blockers (H2RBs) on the plasma concentration of erlotinib and erlotinib-induced adverse reaction in patients ...

OBJECTIVE: An increased slowing of cardiac conduction induced by sodium channel blockers is remarkably observed in carriers of an Asian-specific promoter haplotype [haplotype B (HapB)] of the cardiac sodium channel gene (SCN5A). We investigated the effect of HapB on the therapeutic range for serum flecainide concentration in Asian patients.

PATIENTS AND METHODS: We examined the serum concentration and antiarrhythmic efficacy of flecainide, together with the SCN5A promoter haplotype, in ...

Plasma concentrations of dabigatran, an active principle of prodrug dabigatran etexilate (DABE), are increased by renal impairment (RI) or coadministration of a P-glycoprotein inhibitor. Because the combined effects of drug-drug interactions and RI have not been evaluated by means of clinical studies, the decision of DABE dosing for RI patients receiving P-glycoprotein inhibitors is empirical at its best. We conducted virtual drug-drug interactions studies between DABE and the ...

Majority of bioequivalence studies are conducted in healthy volunteers. It has been argued that bioequivalence may not necessarily hold true in relevant patient populations due to a variety of reasons which affect one formulation more than the other for instance in achlorhydric patients where elevated gastric pH may lead to differential effects on formulations which are pH-sensitive with respect to release or dissolution. We therefore examined achlorhydria-related disparity in ...

OBJECTIVE: To investigate the association between age-related decline in flecainide clearance and CYP2D6 genotype, we conducted a population pharmacokinetic analysis of flecainide using routine therapeutic drug monitoring data.

METHODS: Population pharmacokinetic analysis was performed on retrospective data from 163 genotyped patients treated with oral flecainide for supraventricular tachyarrhythmias. The CYP2D6 genotype was categorized as CYP2D6 homozygous extensive metabolizers ...

ObjectiveWe examined the effect of gender-associated differences in pharmacokinetics on the anti-arrhythmic effects of flecainide in Japanese patients with supraventricular tachyarrhythmia and in healthy subjects.MethodsThe study population comprised 72 outpatients (52 males and 20 females) treated with oral flecainide for supraventricular tachyarrhythmias. Serum flecainide concentrations were determined by use of high-performance liquid chromatography. The anti-arrhythmic efficacy of ...

OBJECTIVES: The aim was to compare blood tacrolimus concentrations in anaemic patients between affinity column-mediated immunoassay (ACMIA) and microparticle enzyme immunoassay (MEIA).

METHODS: Blood concentrations of tacrolimus in 235 whole-blood samples from 64 patients treated with tacrolimus were determined by the two assay methods. Fifty-three samples had low haematocrit (Ht) values (<25%), whereas the other samples had normal Ht values.

KEY FINDINGS: Measured tacrolimus ...

Simultaneous determination of serum flecainide and its oxidative metabolites was carried out by using high performance liquid chromatography (HPLC) equipped with conventional octadecylsilyl silica (ODS) column and fluorescence detector. Flecainide and its metabolites, m-O-dealkylated flecainide (MODF) and m-O-dealkylated lactam of flecainide (MODLF) in serum were extracted with ethyl acetate. The recoveries of flecainide, MODF and MODLF were greater than 92, 93, and 60% with the ...

AIMS: Statistically significant positive correlations are reported for the abundance of hepatic drug-metabolizing enzymes. We investigate, as an example, the impact of CYP3A4-CYP2C8 intercorrelation on the predicted interindividual variabilities of clearance and drug-drug interactions (DDIs) for repaglinide using physiologically based pharmacokinetic (PBPK) modelling.

METHODS: PBPK modelling and simulation were employed using Simcyp Simulator (v15.1). Virtual populations were generated ...

BACKGROUND: Therapeutic drug monitoring (TDM) and dose adjustment of lenvatinib may be beneficial in the treatment of radioiodine-refractory thyroid cancer, by maximizing antitumor effects and minimizing adverse drug reactions. The aim of this study was, therefore, to develop and validate a high-performance liquid chromatography method using an ultraviolet detection system for routine serum lenvatinib detection in patients with thyroid cancer.

METHODS: Serum specimens, spiked with an ...

The reported therapeutic range for trough flecainide concentration is 200-1000 ng mL(-1). Severe adverse events, such as ventricular arrhythmias, have occurred occasionally in patients whose serum flecainide exceeded 1000 ng mL(-1). However, the lower limit remains controversial. We have evaluated blood flecainide concentrations in patients with tachyarrhythmia who received the drug to control palpitation. We measured the flecainide trough levels and incidence and frequency of ...

The chiral inversion kinetics of ibuprofen was evaluated after intraduodenal administration of racemic ibuprofen in conventional powder form and sustained-released granules compared with intravenous administration in rabbits. The AUC ratios of the S-(+) and R-(-) enantiomers remained almost constant values with time up to 2 h after administration of sustained-release formulation, while those after administration of the powder increased with time. R-(-) enantiomer to S-(+) enantiomer ...