Journal Detail Information

1

Cite

Share

Assessment of statistical power for covariate effects in data from phase I clinical trials.

Yukyung KIM ; Hankil SON ; Mijeong SON ; Donghwan LEE ; Young A HEO ; Kyungsoo PARK

Translational and Clinical Pharmacology.2015;23(1):31-34. doi:10.12793/tcp.2015.23.1.31

One of the important purposes in population pharmacokinetic studies is to investigate the relationships between parameters and covariates to describe parameter variability. The purpose of this study is to evaluate the model's ability to correctly detect the parameter-covariate relationship that can be observed in phase I clinical trials. Data were simulated from a two-compartment model with zero-order absorption and first-order elimination, which was built from valsartan's concentration data collected from a previously conducted study. With creatinine clearance (CLCR) being used as a covariate to be tested, 3 different significance levels of 0.001 Absorption ; Clinical Trials, Phase I as Topic* ; Creatinine ; Dataset ; Healthy Volunteers ; Hope

2

Cite

Share

Bioequivalence study of Donepezil hydrochloride in healthy Korean volunteers.

Yewon CHOI ; Su Jin RHEE ; In Jin JANG ; Kyung Sang YU ; Sung Vin YIM ; Bo Hyung KIM

Translational and Clinical Pharmacology.2015;23(1):26-30. doi:10.12793/tcp.2015.23.1.26

Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor that is widely used for treating Alzheimer's disease. This study aimed to compare the pharmacokinetics of Bastia(R), a test tablet formulation of donepezil hydrochloride 10 mg, with those of Aricept(R), the reference tablet formulation of donepezil hydrochloride 10 mg, in healthy Korean male volunteers. A randomized, single-dose, two-way crossover study was conducted in 32 subjects. Subjects received a single dose of either test or reference compound and the alternate drug after a 4-week washout period. Serial blood samples for pharmacokinetic analysis were collected prior to dosing and periodically for 288 h after dosing for measurement of the plasma concentrations of donepezil. A non-compartmental method was used to estimate the pharmacokinetic parameters. The maximum concentration (C(max)) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(288h)) for the two formulations were compared to evaluate bioequivalence. The C(max) of the test and reference drugs were 27.58+/-7.46 and 26.35+/-6.51 microg/L (mean+/-SD), respectively, while AUC(288h) was 1080.14+/-229.77 and 1043.07+/-242.28 microg.h/L (mean+/-SD), respectively. The geometric mean ratios (90% confidence interval) of the C(max) and AUC(288h) of the two tablets were 1.043 (0.990-1.099) and 1.039 (1.013-1.065). In conclusion, the newly formulated tablet of donepezil hydrochloride 10 mg is bioequivalent to the currently marketed 10 mg tablet.
Acetylcholinesterase ; Alzheimer Disease ; Cross-Over Studies ; Humans ; Male ; Pharmacokinetics ; Plasma ; Tablets ; Therapeutic Equivalency* ; Volunteers*

3

Cite

Share

Bioequivalence of the pharmacokinetics between two formulations of 0.2 mg tamsulosin hydrochloride in healthy subjects.

Sang In PARK ; Su Jin RHEE ; In Jin JANG ; Kyung Sang YU ; Sung Vin YIM ; Bo Hyung KIM

Translational and Clinical Pharmacology.2015;23(1):21-25. doi:10.12793/tcp.2015.23.1.21

Tamsulosin is an effective therapeutic option for lower urinary tract symptoms, as it selectively blocks alpha1A- and alpha1D-adrenoceptors in the bladder and prostate. The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics (PK) of two 0.2 mg tamsulosin formulations when administered as the reference formulation (Yuropa(R) sustained-release tablet) vs. the test formulation (Yutanal(R) capsule) in healthy male subjects. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 37 healthy volunteers. The 0.2 mg of tamsulosin as the test or the reference formulation were administered during each period, and serial blood samples were collected up to 36 hours after dosing for PK analyses. A non-compartmental analysis was used to estimate the PK parameters. Geometric mean ratios (GMR) and 90% confidence inter-vals (CIs) were calculated for the two formulations to compare the maximum concentration (Cmax) and the area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast). The mean Cmax and AUClast for the test formulation were 6.19 microg/L and 71.30 microg.h/L, respectively, and 5.76 microg/L and 70.38 microg.h /L for the reference formulation, respectively. The GMRs (90% CIs) of the Cmax and AUClast between the two formulations were 1.09 (1.01-1.17) and 1.03 (0.96-1.10), respectively. Tamsulosin 0.2 mg as the test formulation exhibited bioequivalent PK profiles to those of the reference formulation. Therefore, the test formulation is expected to be an alternative to the reference formulation without concerns about differences in drug exposure.
Cross-Over Studies ; Healthy Volunteers ; Humans ; Lower Urinary Tract Symptoms ; Male ; Pharmacokinetics* ; Prostate ; Therapeutic Equivalency* ; Urinary Bladder

4

Cite

Share

Clinical pharmacology review for primary health care providers: II. Steroids.

Seunghoon HAN

Translational and Clinical Pharmacology.2015;23(1):15-20. doi:10.12793/tcp.2015.23.1.15

Primary health care providers play a critical role in maintaining public health, and the appropriate prescription of pharmaceutical products is a major component of their practice. This series of articles entitled 'Clinical Pharmacology Review for Primary Health Care Providers' is intended to help primary health care providers select more appropriate prescriptions for frequently used drugs based on up-to-date information. We expect that this effort will contribute to improvements in public health and diminish unnecessary drug use.
Drug Interactions ; Pharmaceutical Preparations ; Pharmacology ; Pharmacology, Clinical* ; Prescriptions ; Primary Health Care* ; Public Health ; Steroids*

5

Cite

Share

Statistical basis for pharmacometrics: maximum likelihood estimator and its asymptotics.

Kyungmee CHOI ; Dong Seok YIM

Translational and Clinical Pharmacology.2015;23(1):8-14. doi:10.12793/tcp.2015.23.1.8

The maximum likelihood estimator is the point estimator of the top priority in statistical data analysis because of its optimum properties for large sample size. While the maximum likelihood estimator is widely used, it has been an abstruse subject for pharmacometricians without statitics bagkround because of high dimensional calculus and asymptotic theories. This tutorial provides a general and brief introduction to the maximum likelihood estimator and its related caluculus for non-statisticians.
Calculi ; Data Interpretation, Statistical ; Sample Size

6

Cite

Share

R-based reproduction of the estimation process hidden behind NONMEM(R) Part 1: first-order approximation method.

Min Gul KIM ; Dong Seok YIM ; Kyun Seop BAE

Translational and Clinical Pharmacology.2015;23(1):1-7. doi:10.12793/tcp.2015.23.1.1

NONMEM(R) is the most-widely used nonlinear mixed effects modelling tool introduced into population PK/PD analysis. Even though thousands of pharmaceutical scientists utilize NONMEM(R) routinely for their data analysis, the various estimation methods implemented in NONMEM(R) remain a mystery for most users due to the complex statistical and mathematical derivations underlying the algorithm used in NONMEM(R). In this tutorial, we demonstrated how to directly obtain the objective function value and post hoc eta for the first order approximation method by the use of R. We hope that this tutorial helps pharmacometricians understand the underlying estimation process of nonlinear mixed effects modelling.
Hope ; Reproduction* ; Statistics as Topic

7

Cite

Share

Comparison of pharmacokinetic characteristics of sildenafil citrate chewable tablets and film-coated tablets in healthy male subjects.

Hyounggyoon YOO ; Sang Min CHO ; Youn Woong CHOI ; Hye Jung LEE ; Ji Hye KWON ; Soo Whan KIM ; Jae Woo KIM ; SeungHwan LEE ; Jang Hee HONG

Translational and Clinical Pharmacology.2017;25(3):153-156. doi:10.12793/tcp.2017.25.3.153

UI14SDF100CW is a chewable tablet of sildenafil citrate, which was developed to improve compliance through convenience of administration. The purpose of this study was to compare the pharmacokinetic (PK) properties of sildenafil citrate chewable tablets (UI14SDF100CW) and conventional sildenafil citrate film-coated tablets (Viagra®, Pfizer). A randomized, open-label, single dose, two-treatment, two-period, two-way crossover study was conducted in 60 healthy male volunteers. In each period, the subjects received a single oral dose of UI14SDF100CW or Viagra® (both tablets contain 140.45 mg of sildenafil citrate, which is equivalent to 100 mg of sildenafil). Serial blood samples were collected up to 24 h post-dose for PK analysis. The plasma concentration of sildenafil was determined using a validated HPLC-MS/MS assay. PK parameters of sildenafil were calculated using non-compartmental methods. The plasma concentration-time profiles of sildenafil in both formulations were similar. For UI14SDF100CW, the C(max) and AUC(last) of sildenafil were 1068.69 ± 458.25 (mean ± standard deviation) mg/L and 3580.59 ± 1680.29 h·mg/L, and the corresponding values for Viagra® were 1146.84 ± 501.70 mg/L and 3406.35 ± 1452.31 h·/L, respectively. The geometric mean ratios (90% confidence intervals) of UI14SDF100CW to Viagra® for C(max) and AUC(last) were 0.933 (0.853–1.021) and 1.034 (0.969–1.108), respectively, which met the bioequivalence criteria of Korean regulatory agency. In conclusion, UI14SDF100CW and Viagra® showed similar PK properties. Therefore, UI14SDF100CW can be an alternative to sildenafil for the treatment of erectile dysfunction, providing better compliance.
Compliance ; Cross-Over Studies ; Erectile Dysfunction ; Humans ; Male* ; Pharmacokinetics ; Plasma ; Sildenafil Citrate* ; Tablets* ; Therapeutic Equivalency ; Volunteers

8

Cite

Share

Prediction and visualization of CYP2D6 genotype-based phenotype using clustering algorithms.

Eun Young KIM ; Sang Goo SHIN ; Jae Gook SHIN

Translational and Clinical Pharmacology.2017;25(3):147-152. doi:10.12793/tcp.2017.25.3.147

This study focused on the role of cytochrome P450 2D6 (CYP2D6) genotypes to predict phenotypes in the metabolism of dextromethorphan. CYP2D6 genotypes and metabolic ratios (MRs) of dextromethorphan were determined in 201 Koreans. Unsupervised clustering algorithms, hierarchical and k-means clustering analysis, and color visualizations of CYP2D6 activity were performed on a subset of 130 subjects. A total of 23 different genotypes were identified, five of which were observed in one subject. Phenotype classifications were based on the means, medians, and standard deviations of the log MR values for each genotype. Color visualization was used to display the mean and median of each genotype as different color intensities. Cutoff values were determined using receiver operating characteristic curves from the k-means analysis, and the data were validated in the remaining subset of 71 subjects. Using the two highest silhouette values, the selected numbers of clusters were three (the best) and four. The findings from the two clustering algorithms were similar to those of other studies, classifying *5/*5 as a lowest activity group and genotypes containing duplicated alleles (i.e., CYP2D6*1/*2N) as a highest activity group. The validation of the k-means clustering results with data from the 71 subjects revealed relatively high concordance rates: 92.8% and 73.9% in three and four clusters, respectively. Additionally, color visualization allowed for rapid interpretation of results. Although the clustering approach to predict CYP2D6 phenotype from CYP2D6 genotype is not fully complete, it provides general information about the genotype to phenotype relationship, including rare genotypes with only one subject.
Alleles ; Classification ; Cluster Analysis* ; Cytochrome P-450 CYP2D6* ; Dextromethorphan ; Genotype ; Metabolism ; Phenotype* ; ROC Curve

9

Cite

Share

Caffsim: simulation of plasma caffeine concentrations implemented as an R package and Web-applications.

Sungpil HAN ; Yong Soon CHO ; Seok Kyu YOON ; Hyungsub KIM ; Kyun Seop BAE

Translational and Clinical Pharmacology.2017;25(3):141-146. doi:10.12793/tcp.2017.25.3.141

Caffeine is a naturally-occurring central nervous system stimulant found in plant constituents including coffee, cocoa beans, and tea leaves. Consumption of caffeine through imbibing caffeinated drinks is rapidly growing among children, adolescents, and young adults, who tend to be more caffeine-sensitive than the rest of the general public; consequently, caffeine-related toxicities among these groups are also growing in number. However, a quantitative and interactive tool for predicting the plasma caffeine concentration that may lead to caffeine intoxication has yet to be developed. Using the previously established population-pharmacokinetic model, we developed “caffsim” R package and its web-based applications using Shiny and EDISON (EDucation-research Integration through Simulation On the Net). The primary aim of the software is to easily predict and calculate plasma caffeine concentration and pharmacokinetic parameters and visualize their changes after single or multiple ingestions of caffeine. The caffsim R package helps understand how plasma caffeine concentration changes over time and how long toxic concentration of caffeine can last in caffeine-sensitive groups. It may also help clinical evaluation of relationship between caffeine intake and toxicities when suspicious acute symptoms occur.
Adolescent ; Cacao ; Caffeine* ; Central Nervous System ; Child ; Coffee ; Humans ; Pharmacokinetics ; Plants ; Plasma* ; Tea ; Young Adult

10

Cite

Share

Hemorrhagic pericarditis associated with rivaroxaban in an atrial fibrillation patient with pacemaker.

Shi Hyun RHEW ; Sung Soo KIM

Translational and Clinical Pharmacology.2017;25(3):138-140. doi:10.12793/tcp.2017.25.3.138

Rivaroxaban is a new oral anticoagulant used for the prevention of stroke in patients with atrial fibrillation. Hemorrhagic pericarditis is known to occur with rivaroxaban; however, only a few case reports in the literature describe such events. Recently, we experienced hemorrhagic pericarditis that treated with rivaroxaban for anticoagulation of newly diagnosed, non valvular AF patients with pacemaker. An 83 year old male with permanent pacemaker receiving rivaroxaban 20 mg daily once for 3 months presented at our emergency department complaining of exertional dyspnea. ECG showed intermittent atrial pacing failure and echocardiography showed large amount of pericardial effusion. After urgent pericardiocentesis, which resulted in removal of 500cc bloody fluid, there was an immediate and dramatic improvement in the patient's clinical state. He was discharged without anticoagulation therapy due to concern for further bleeding. This case highlight the potential for bleeding complications associated with novel anticoagulants. Rivaroxaban is being used with increasing frequently in outpatient care. However, no available laboratory test specifically measures the anticoagulant effect of rivaroxaban. Also, in the events of serious bleeding, no specific antidotes, reversal agents were available. Clinicians should be aware of the possibility of hemopericardium in patients treated with anticoagulants, including rivaroxaban who presented with cardiomegaly.
Ambulatory Care ; Anticoagulants ; Antidotes ; Atrial Fibrillation* ; Cardiomegaly ; Dyspnea ; Echocardiography ; Electrocardiography ; Emergency Service, Hospital ; Hemorrhage ; Humans ; Male ; Pericardial Effusion ; Pericardiocentesis ; Pericarditis* ; Rivaroxaban* ; Stroke

DISPLAY OPTIONS

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share

Cite

Share