Prediction of the human antiplatelet effect of S- and R-indobufen using population pharmacodynamic modeling and simulation based on platelet aggregation test.

Indobufen (Ibustrin®), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using NONMEM® and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L.

Effects of Renal Impairment on the Pharmacokinetics and Safety of Udenafil.

Udenafil is a phosphodiesterase-5 inhibitor used to treat erectile dysfunction. Although udenafil is not predominantly eliminated by the kidney, renal impairment can alter its secretion/transport pathways. Drug pharmacokinetics and safety must therefore be assessed in subjects with a renal impairment.

Pharmacokinetics of a Cholesterol-conjugated Aptamer Against the Hepatitis C Virus (HCV) NS5B Protein.

Hepatitis C virus (HCV) is the major cause of progressive liver disease such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Previously, we reported that a 29 nucleotide-long 2'-F pyrimidine modified RNA aptamer against the HCV nonstructural protein 5B efficiently inhibited HCV replication and suppressed HCV infectious virus particle formation in a cell culture system. In this study, we modified this aptamer through conjugation of cholesterol for in vivo availability.

Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats.

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple- or single-dose oral and transdermal administration. Venous blood was collected at preset intervals in single- and multiple-dose studies.

Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study.

Background: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR) formulation in healthy male subjects.

Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects.

Predicting the efficacy of an oral paclitaxel formulation (DHP107) through modeling and simulation.

Purpose: DHP107 is an oral paclitaxel under development. The present study characterized the pharmacokinetic properties of DHP107 and predicted the efficacy in comparison to that of intravenous paclitaxel, using modeling and simulation of data from the early phase of clinical development.

Methods: In the first-in-human study of the pharmacokinetic characteristics of DHP107 and intravenous paclitaxel, patients received DHP107 60 to 600 mg/m(2), followed by intravenous paclitaxel 175 mg/m(2).

Tolerability and pharmacokinetics of two formulations of megestrol acetate under fed conditions in healthy volunteers.

Purpose: Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers.

Pharmacokinetic, pharmacodynamic, and safety/tolerability profiles of CG100649, a novel COX-2 inhibitor: results of a phase i, randomized, multiple-dose study in healthy Korean men and women.

Background: CG100649 is a novel anti-inflammatory drug that is currently under development. CG100649 demonstrates a dual mechanism of action on cyclooxygenase-2 and carbonic anhydrase that may result in favorable treatment effects and few adverse gastrointestinal and cardiovascular events.

Objective: The objective of this study was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of administering multiple oral doses of CG100649 to healthy Korean volunteers.

Population pharmacokinetic analysis of simvastatin and its active metabolite with the characterization of atypical complex absorption kinetics.

Purpose: The pharmacokinetics of simvastatin is complex with multiple peaks in the absorption phase, which cannot be adequately described by a conventional first order absorption model. The biotransformation of simvastatin into simvastatin acid, an active metabolite, is reversible. This study evaluated the pharmacokinetics of simvastatin and simvastatin acid, focusing on the absorption kinetics.

Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

Objectives: For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets.

Materials And Methods: This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers.

Effects of ketoconazole on the pharmacokinetic properties of CG100649, a novel NSAID: a randomized, open-label crossover study in healthy Korean male volunteers.

Background: CG100649, a novel selective cyclooxygenase-2 inhibitor that also inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk typical of other NSAIDs. Concurrent medications may influence the activities of the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized.

Objectives: This study was designed to evaluate the influence of ketoconazole, a known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649.

Pharmacokinetics, tolerability, and safety of the single oral administration of AGSAV301 vs Exforge: a randomized crossover study of healthy male volunteers.

Background And Objective: Valsartan, an angiotensin receptor blocker, is often used with calcium channel blockers (CCBs) such as amlodipine to control hypertension. Recently, the fixed-dose combination (FDC) of amlodipine 10 mg/valsartan 160 mg (Exforge) was approved. Amlodipine is a racemic mixture of CCB; S-amlodipine has higher activity than R-form.

Pharmacokinetic interactions between eperisone hydrochloride and aceclofenac: a randomized, open-label, crossover study of healthy Korean men.

Background: Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs.

Evaluation of pharmacokinetic and pharmacodynamic profiles and tolerability after single (2.5, 5, or 10 mg) and repeated (2.5, 5, or 10 mg bid for 4.5 days) oral administration of ivabradine in healthy male Korean volunteers.

Background: Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure heart rate (HR)-reducing effects with anti-ischemic efficacy as well as improvement in heart failure outcomes.

Objective: The purpose of this study was to explore pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and tolerability in healthy male Korean volunteers, as well as to compare them with PK/PD profiles of white subjects.

Methods: This was a randomized, double-blind, placebo-controlled Phase I study conducted in healthy male subjects.

Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via modeling and simulation analysis in a D2 receptor occupancy study.

Purpose: To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development.

Methods: In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days.

Assessment of the influence of severe renal impairment on the pharmacokinetics of mirodenafil in Korean male volunteers.

Objective: To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers.

Methods And Materials: This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS.

Bioavailability and tolerability of combination treatment with revaprazan 200 mg + itopride 150 mg: a randomized crossover study in healthy male Korean volunteers.

Background: To date, no definitive treatment of functional dyspepsia (FD) has been proven to be effective and reasonably well-tolerated. Proton pump inhibitors (PPIs) combined with prokinetic agents are considered an effective option. Revaprazan is a selective potassium-competitive acid blocker that reversibly inhibits gastric H(+)/K(+)-ATPase and shows effective acid suppression comparable to PPIs.

A single-dose, crossover study comparing the pharmacokinetics and pharmacodynamics of 2 formulations of metformin in healthy volunteers.

Objective: To compare pharmacokinetics and pharmacodynamics of two formulations of metformin in healthy male volunteers under fasting conditions.

Methods And Materials: This was a randomized, 3-treatment, 6-sequence, 3-period, crossover study in healthy Korean volunteers. Subjects received a placebo or a single oral dose of reference formulation (500-mg metformin hydrochloride) or a test formulation (571-mg metformin acetate).

The pharmacokinetics of letrozole: association with key body mass metrics.

Purpose: To characterize the pharmacokinetics (PK) of letrozole by noncompartmental and mixed effect modeling analysis with the exploration of effect of body compositions on the PK.

Methods: The PK data of 52 normal healthy male subjects with intensive PK sampling from two separate studies were included in this analysis. Subjects were given a single oral administration of 2.

Pharmacokinetic interaction of telmisartan with s-amlodipine: an open-label, two-period crossover study in healthy Korean male volunteers.

Background: Telmisartan belongs to a class of orally active angiotensin II receptor blockers (ARBs), and S-amlodipine is an enantiomer of amlodipine. Amlodipine is a racemic mixture and the calcium channel blocking (CCB) effect is confined to S-amlodipine, whereas R-amlodipine has a 1000-fold lower activity and no racemization occurs in vivo in human plasma. Combination therapy of ARBs with CCBs provides advantages for blood pressure control and vascular protection over monotherapy.

Effects of ketoconazole and rifampicin on the pharmacokinetics of gemigliptin, a dipeptidyl peptidase-IV inhibitor: a crossover drug-drug interaction study in healthy male Korean volunteers.

Background: Gemigliptin (LC15-0444) is a newly developed selective and competitive inhibitor of dipeptidyl peptidase (DPP)-4 and has potential for the treatment of type 2 diabetes mellitus. Gemigliptin is metabolized by the cytochrome P450 (CYP) 3A4 isozyme to yield the active major metabolite LC15-0636.

Objective: The effects of multiple oral doses of ketoconazole (a potent CYP3A4 inhibitor) and multiple oral doses of rifampicin (a potent CYP3A4 inducer) on the pharmacokinetic properties of a single oral dose of gemigliptin were evaluated in fasting healthy male Korean volunteers.

Pharmacokinetic interaction between pitavastatin and valsartan: a randomized, open-labeled crossover study in healthy male Korean volunteers.

Background: Pitavastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and valsartan, an angiotensin receptor blocker, are used concurrently in some patients who are both hyperlipidemic and hypertensive. However, to date, no published studies have explored whether there is an interaction between pitavastatin and valsartan.

Objective: The aim of this study was to investigate the potential pharmacokinetic interaction between pitavastatin and valsartan in healthy male volunteers in Korea.

Pharmacokinetic comparison of 2 formulations of anastrozole (1 mg) in healthy Korean male volunteers: a randomized, single-dose, 2-period, 2-sequence, crossover study.

Background: Anastrozole is an aromatase inhibitor used to treat advanced breast cancer in postmenopausal women. A generic 1-mg tablet of anastrozole was recently developed.

Objective: The study was designed to provide data to submit to Korean regulatory authorities to allow marketing of the test formulation.

Pharmacokinetic comparison of controlled- and immediate-release formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers.

Background: Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen. A new extended-release form of dexibuprofen has recently been developed.

Objective: We aimed to compare pharmacokinetic characteristics of controlled-release (CR) and immediate-release (IR) formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers.