Evaluation of Age-Related Changes in Teneligliptin Pharmacokinetics in Japanese and European Descent Subjects Using a Physiologically Based Pharmacokinetic Model.

Introduction: Drugs often show differing pharmacokinetic (PK) profiles, such as higher plasma concentrations, in older people than in younger people owing to age-related decreases in physiological functions. However, it is difficult to evaluate the PK in older populations. Therefore, we simulated the plasma age-related changes in the PK of teneligliptin, a dipeptidyl peptidase-4 inhibitor, using physiologically based PK (PBPK) models.

Drug-Drug Interactions of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone With Midazolam, Warfarin, and Digoxin: A Phase 1 Studies in Healthy Volunteers.

Purpose: To characterize the clinical relevance of in vitro drug-drug interaction findings with apararenone (MT-3995), the effects of apararenone on the sensitive substrates of cytochrome P450 3A4 (midazolam) and 2C9 (warfarin), and P-glycoprotein (digoxin), were assessed through a series of studies conducted in healthy volunteers.

Methods: Three studies were conducted in 56 healthy adults. Study 1 investigated the effects of the administration of apararenone with midazolam; apararenone was administered on days 2 (320 mg) and days 3-15 (20 mg/d), and midazolam 2 mg, on days 1 and 15.

Collaborations between Clinical Pharmacologists in Japan and in the United States - Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan.

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Clinical Pharmacology Leadership Group (CPLG) held its first meeting of Japan-based representatives at Astellas Pharma headquarters in Tokyo on October 1, 2019. The meeting was also attended by Japan Pharmaceutical Manufactures Association (JPMA) Clinical Pharmacology Task Force (CPTF) members. Overall, nearly 30 clinical pharmacologists representing 14 companies attended the event.

Phase 1 Studies to Define the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone in Healthy Volunteers.

Apararenone is a long-acting, nonsteroidal mineralocorticoid receptor antagonist (MRA). The safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single- and multiple-dose apararenone were assessed in 3 phase 1 randomized, double-blind studies in 223 healthy adults. Study 1 assessed the PK, safety/tolerability, and PD of single-dose apararenone (3.

Absorption, disposition and metabolic pathway of amiselimod (MT-1303) in healthy volunteers in a mass balance study.

The absorption, metabolism and excretion of MT-1303 were investigated in healthy male subjects after a single oral dose of 0.4 mg [14C]-MT-1303 (ClinicalTrials.gov NCT02293967).

Pharmacokinetic profile of edaravone: a comparison between Japanese and Caucasian populations.

Background: Amyotrophic lateral sclerosis (ALS) affects persons of all races, and there continues to be a need for effective therapies to treat the disease.

Objective: To compare the pharmacokinetics (PK) of edaravone between Japanese and Caucasian populations.

Methods: Data from five PK studies among Japanese and Caucasian healthy volunteers were pooled and evaluated.

Effect of ketoconazole on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor teneligliptin: an open-label study in healthy white subjects in Germany.

Objective: The aim of this study was to examine the effect of ketoconazole, a potent cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) inhibitor, on teneligliptin pharmacokinetics and to evaluate the safety of combined administration of teneligliptin with ketoconazole.

Methods: This open-label, fixed-sequence study was conducted in 16 healthy adult volunteers in Germany. On day 1, under fasting conditions, 20 mg of teneligliptin was administered to evaluate the pharmacokinetics of teneligliptin alone.

Tolerability, pharmacokinetics and pharmacodynamics of TA-8995, a selective cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.

Aims: Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.

Methods: Study 1: Subjects received single doses of TA-8995 or placebo (fasted). Doses were 5, 10, 25, 50 (fed/fasted), 100 and 150 mg (Caucasian males, 18-55 years), 25 mg (Caucasian males, > 65 years and Caucasian females, 18-55 years), 25, 50, 100 and 150 mg (Japanese males, 18-55 years).

Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin in humans.

1. The absorption, metabolism and excretion of teneligliptin were investigated in healthy male subjects after a single oral dose of 20 mg [(14)C]teneligliptin. 2.

A comparative pharmacokinetic study of recombinant human serum albumin with plasma-derived human serum albumin in patients with liver cirrhosis.

We conducted an open-label, parallel-group study of the high purity, mass-produced recombinant human serum albumin (rHSA), derived from the methylotrophic yeast Pichia pastoris, to compare pharmacokinetics and ensure bioequivalence with plasma-derived human serum albumin (pHSA) in 22 patients with liver cirrhosis. Both rHSA and pHSA groups enrolled 11 patients each, assigned according to predose serum albumin concentrations using the minimization method. Pharmacokinetic and safety profiles for 3-day repeated intravenous infusions at a daily dose of 25 g were evaluated for 8 days.

Clearance of imidapril, an Angiotensin-converting enzyme inhibitor, during hemodialysis in hypertensive renal failure patients: comparison with quinapril and enalapril.

The dialyzability of imidaprilat, an active metabolite of the angiotensin-converting enzyme (ACE) inhibitor imidapril, was determined and compared with those of enalaprilat and quinaprilat in hypertensive patients on chronic hemodialysis. Imidapril (5 mg/d, n = 6), enalapril (2.5 mg/d, n = 6), or quinapril (2.

Favorable effect on postgraduate clinical practice of a drug-interaction exercise for undergraduate students.

Aim: Undergraduate students in Jichi Medical School participated in a laboratory exercise investigating the furosemide-probenecid interaction at the end of their clinical pharmacology (CP) course. The aim of this study was to determine whether they learned to recognize drug interactions better than students who did not take such a course.

Methods: We conducted a postal survey of physicians who had graduated from Jichi Medical School or from other medical schools without a CP course including the exercise.

Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam.

Objective: Grapefruit juice (GFJ) inhibits cytochrome P450 (CYP) 3A4 in the gut wall and increases blood concentrations of CYP3A4 substrates by the enhancement of oral bioavailability. The effects of GFJ on two benzodiazepine hypnotics, triazolam (metabolized by CYP3A4) and quazepam (metabolized by CYP3A4 and CYP2C9), were determined in this study.

Methods: The study consisted of four separate trials in which nine healthy subjects were administered 0.

Drug interaction between St John's Wort and quazepam.

Aim: St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined.

Methods: Thirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day(-1)) or placebo for 14 days.

SOFA score predicts postoperative outcome of patients with colorectal perforation.

Background/aims: Colorectal perforation remains a life-threatening condition associated with high mortality. Various factors and operative procedures have been discussed in regard to prediction of outcome, and several scoring systems have been proposed to predict the outcome of critically ill patients. The present study was undertaken to identify factors and determine predictive scoring systems for the postoperative outcome of patients with colorectal perforation.

Partial protective effect of Y-27632, a Rho kinase inhibitor, against hepatic ischemia-reperfusion injury in rats.

(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)-cyclohexanecarboxamide dihydrochloride (Y-27632), a Rho kinase inhibitor, has a suppressive effect on the functions of polymorphonuclear leukocytes. In this study, the influence of Y-27632 on ischemia-reperfusion injury of the liver was examined in rats. Y-27632 (3 mg/kg) or vehicle alone was intravenously injected into rats 60 min before occlusion.

Inhibition of Rho-kinase reduces renal Na-H exchanger activity and causes natriuresis in rat.

Rho-kinase regulates the actin cytoskeleton and therefore modulates transport. The role of Rho-kinase in Na-H exchanger (NHE) activity of rat proximal convoluted tubules (PCTs) was investigated using (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), a specific inhibitor of Rho-kinase. In spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, apical and basolateral NHE activities were determined by measuring cell pH recovery following luminal NH4+ prepulse and basolateral sodium removal, respectively.

Vitamin E-bonded hemodialyzer improves neutrophil function and oxidative stress in patients with end-stage renal failure.

We evaluated the biocompatibility of a newly developed vitamin E hemodialyzer (CL-EE; Terumo Co Ltd, Tokyo, Japan) by neutrophil function and oxidant stress in patients with end-stage renal failure in a randomized crossover study. Ten patients underwent hemodialysis using either the CL-EE or a control dialyzer membrane identical to the CL-EE except for vitamin E binding for 12 weeks in a crossover fashion after a 1-month washout period with hemophane membranes. White blood cell counts, serum oxidized low-density lipoprotein (Ox-LDL) levels, and malondialdehyde (MDA) levels during hemodialysis sessions were measured at the initiation and end of the CL-EE and control trials.