This report focuses on the adaptive phase I trial design aimed to find clinically applicable dose for decitabine maintenance treatment after allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome and secondary acute myeloid leukemia. The first cohort (three patients) was given same initial daily of (5 mg/m2/day, five consecutive days 4-week intervals). In all cohorts, doses Cycles 2 4 were individualized using pharmacokinetic-pharmacodynamic...

Colistin is increasingly used as a salvage therapy for nosocomial infections caused by multidrug-resistant Gram-negative bacteria such Pseudomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data colistin are limited to guide dosing. The aim of this study was develop population PK model identify optimal dosage regimens burn patients. Fifty patients with burns ranging from 4% 85% total body surface area who had been treated colistimethate sodium (CMS)...

ABSTRACT Piperacillin in combination with tazobactam, a β-lactamase inhibitor, is commonly used intravenous antibiotic for the empirical treatment of infection intensive care patients, including burn patients. The purpose this study was to develop population pharmacokinetic (PK) model piperacillin patients and predict probability target attainment (PTA) using MICs concentrations simulated from PK model. Fifty treated piperacillin-tazobactam were enrolled. Piperacillin-tazobactam administered...

The pharmacokinetic (PK) property of fluconazole might be significantly altered in major burn patients by medical interventions and physiologic changes. In this study, our aims were to investigate PK using a population approach recommend the optimal regimen based upon predicted therapeutic outcome. At steady state, blood samples for analysis obtained from 60 receiving between 100 ~400 mg daily. A mixed-effect modeling was performed outcome antifungal therapy 10,000 virtual NONMEM (version...

The usefulness of pharmacokinetics bortezomib for multiple myeloma (MM) with respect to the maximum response and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum subcutaneous therapy BIPN occurrence first 12 weeks treatment in 35 MM patients treated by bortezomib–dexamethasone (VD) bortezomib–melphalan–prednisone (VMP) were evaluated. On day 1 cycle 1, seven whole-blood samples collected 3 h after dosing completion obtain plasma concentration area under...

Abstract Extracorporeal membrane oxygenation (ECMO) is associated with pharmacokinetic (PK) changes of drugs. It presents considerable challenges to providing optimal dosing regimens for patients receiving ECMO. We aimed describe the population PK remifentanil in critically ill adult venoartrial extracorporeal (VA-ECMO) and identify determinants altered concentrations. The model was developed using nonlinear mixed effects modelling (NONMEM). Fifteen who received a continuous infusion during...

We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using mixed effect analysis method (NONMEM, Ver. 6.2), as well conventional non-compartmental method. also examined safety and tolerability. The PK used plasma concentrations day 1 14. There was no observed accumulation extract. typical point estimates were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption...

Abstract: A single 400 mg dose of moxifloxacin has been the standard positive control for thorough QT (TQT) studies. However, it is not clearly known whether a also applicable to TQT studies in Asian subjects, including Koreans. Thus, we aimed develop pharmacokinetic (PK)-pharmacodynamic (PD) model moxifloxacin, evaluate time course its effect on intervals Data from three 33 healthy male Korean subjects who received and 800 placebo (water) were used. Twelve-lead electrocardiograms taken 2...

Background: Esomeprazole is the most effective treatment for acid-related disorders and widely used with enteric coating due to rapid degradation in acidic environment. However, enteric-coated formulation delays absorption onset of action. To overcome this limitation, an immediate-release containing esomeprazole 20 mg sodium bicarbonate 800 (IR-ESO) was developed. Purpose: evaluate safety, pharmacokinetics (PK), pharmacodynamics IR-ESO compared those (ESO). Methods: A randomized, open-label,...

Atorvastatin and ezetimibe are frequently co-administered to treat patients with dyslipidemia for the purpose of low-density lipoprotein cholesterol control. However, pharmacokinetic (PK) drug interaction between atorvastatin has not been evaluated in Korean population. The aim this study was investigate PK two drugs healthy volunteers. An open-label, randomized, multiple-dose, three-treatment, three-period, Williams design crossover conducted 36 male subjects. During each period, subjects...

The structural complexity of crossover studies for bioequivalence test confuses analysts and leaves them a hard choice among various programs. Our study reviews PROC GLM MIXED in SAS compares widely used codes studies. based on REML is more recommended since it provides best linear unbiased estimator the random between-subject effects its variance. also considers covariance structure within subject over period which most PK/PD ignore. QT interval data after administra tion moxifloxacin fixed...

Abstract GC 1118 is an anti‐epidermal growth factor receptor ( EGFR ) monoclonal antibody that currently under clinical development. In this study, the pharmacokinetics PK of were modelled in monkeys to predict human and occupancy RO profiles. The serum concentrations its comparator (cetuximab) assessed with a non‐compartmental analysis target‐mediated drug disposition TMDD model after intravenous infusion (3–25 mg/kg) these drugs. scaling exponent synthesis rate was determined using...

Izuforant is a selective, and potent histamine H4 receptor (H4R) antagonist developed to treat atopic dermatitis (AD). There an unmet medical need for therapeutic agents control inflammation pruritus. strong candidate this task based on the findings of non-clinical studies showing that inhibition histamine-mediated signaling pathway via H4R by izuforant results in decreased pruritus inflammation. This study aimed evaluate clinical pharmacokinetic (PK) pharmacodynamic (PD) profiles izuforant....

Abstract Background In this study, we developed a pharmacokinetic (PK)- pharmacodynamic (PD) model of new sustained release formulation interferon-α-2a (SR-IFN-α) using the blood concentration IFN-α and neopterin in order to quantify magnitude saturation production over time healthy volunteers. The SR-IFN-α study is solid microparticular manufactured by spray drying feeding solution containing IFN-α, biocompatible polymer (polyethylene glycol) sodium hyaluronate. Methods full PK PD...

Abstract: Pregabalin is an anticonvulsant used for the treatment of neuropathic pain and partial seizure in adults. The aim this study was to develop a population pharmacokinetic (PK) model describe absorption characteristics pregabalin given fasted or after meals. Data from five healthy subject PK studies (n=88) single- multiple-dose (150 mg) were used. administered twice daily, without meals 30 min meal (regular high-fat diet) morning 4 h evening. Serial plasma samples collected up 24 last...

Background: Levodropropizine is non-opioid agent whose peripheral antitussive action may result from its modulation of sensory neuropeptide levels. Currently, levodropropizine 60 mg taken three-times daily. A controlled release formulation (levodropropizine CR) 90 was developed, which can be twice The aim this study to evaluate the safety and pharmacokinetic characteristics after multiple oral administrations CR tablets in healthy male volunteers. Methods: randomized, open-label, cross-over...

Evogliptin (EV) is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for glycemic control in patients with type 2 diabetes mellitus (T2DM). This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between EV sodium glucose cotransporter-2 inhibitors (SGLT2i) healthy volunteers since combination therapy of DPP4i SGLT2i has been considered as an effective option T2DM treatment. A randomized, open-label, multiple-dose, two-arm, three-period, three treatments,...

It was recently reported that the Cmax and AUC of rosuvastatin increases when it is coadministered with telmisartan cyclosporine. Rosuvastatin known to be a substrate OATP1B1, OATP1B3, NTCP, BCRP transporters. The aim this study explore mechanism interactions between two perpetrators, Published (cyclosporine) or newly developed (telmisartan) PBPK models were used end. model in Simcyp (version 15)'s drug library modified reflect racial differences exposure. In telmisartan–rosuvastatin case,...

Purpose: Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim ® recombinant filgrastim product tested for biosimilarity its reference product, Neupogen . We conducted comparative clinical trial of the 2 products. Patients and methods: A randomized, open-label, 2-way crossover, single-dose Phase I study was 56 healthy subjects. After 5 10 μg/kg single subcutaneous administration test pharmacokinetic...

YH4808 is a novel potassium-competitive acid blocker that was developed as therapeutic agent for gastric acid-related diseases; it may replace proton pump inhibitors, which are widely used in combination with amoxicillin and clarithromycin Helicobacter pylori eradication. We compared the pharmacokinetic (PK) profiles safety of amoxicillin, clarithromycin, monotherapies or evaluating potential drug interactions. An open-label, randomized, single-dose, Latin-square (4 × 4) crossover study...

BR-TD-1001 was developed as a booster for the immunity maintenance of diphtheria and tetanus. The aim this study to evaluate safety immunogenicity (test vaccine) in comparison with placebo an active comparator healthy Korean adults. A randomized, double-blind, placebo-controlled, comparator, phase I clinical trial conducted. Fifty subjects were randomly assigned one 3 treatment groups ratio 2:2:1, administered single intramuscular dose test vaccine, or placebo, respectively. All monitored 4...