Ethnic Differences in Pharmacokinetics in New Drug Applications and Approved Doses in Japan

Fukunaga, Satoshi; Kusama, Makiko; Arnold, Frank; Ono, Shunsuke

doi:10.1177/0091270010381500

Cited by 22 publications

(26 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, because interethnic differences in PK properties have been reported between East Asian and white populations, the clinical trial results of one group cannot be readily extrapolated to the other. [2][3][4] It also remains unclear whether interethnic differences in PK and PD properties of medications are present among East Asian populations, although East Asian clinical trials have been effective for some high prevalence diseases, such as gastric cancer. 5 Thus, it may be necessary to clarify ethnic differences in PKs and PDs to facilitate the utilization of clinical trial data across East Asian countries, such as Japan, China, and South Korea.…”

Section: Study Highlightsmentioning

confidence: 99%

“…One hundred nineteen healthy male subjects (CYP2C9 genotypes: Japanese, 26 subjects with *1/*1 and 4 subjects with *1/*3; Chinese, 26 subjects with *1/*1, 1 subject with *1/*2, and 3 subjects with *1/*3; Korean, 25 subjects with *1/*1 and 4 subjects with *1/*3; and white, 20 subjects with *1/*1, 5 subjects with *1/*2, 1 subject with *2/*2, and 4 subjects with *1/*3) were administered single oral doses of meloxicam (7.5 mg). 6 Blood samples were collected before and at 1,2,3,4,5,6,8,12,24,36,48,60, and 72 hours after drug administration, and plasma meloxicam concentrations were determined using liquid chromatography-tandem mass spectrometry. 6 The trial was registered in the UMIN Clinical Trials Registry system (UMIN000004173), and the population PK study was approved by the Ethics Committee of the School of Pharmacy, Nihon University.…”

Section: Data Sourcementioning

confidence: 99%

“…In these clinical trials, interethnic differences in pharmacokinetic (PK) and pharmacodynamic (PD) properties should be considered. Moreover, because interethnic differences in PK properties have been reported between East Asian and white populations, the clinical trial results of one group cannot be readily extrapolated to the other . It also remains unclear whether interethnic differences in PK and PD properties of medications are present among East Asian populations, although East Asian clinical trials have been effective for some high prevalence diseases, such as gastric cancer…”

mentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The Role of Ethnicity on Drug Response

Aoyama

Ishida

Kaneko

et al. 2017

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

We aimed to reanalyze the differences in the pharmacokinetics (PKs) of meloxicam in East Asian populations based on a population approach using previously published data and to investigate the factors found in population PK analysis that affect the pharmacodynamics (PDs) of meloxicam. Population PK analysis was performed in 119 healthy male subjects (30 Japanese, 30 Chinese, 29 Korean, and 30 white) under strictly controlled trial conditions with regulated meals and a single lot of the drug. We found that CYP2C9 genotype and lean body mass were statistically significant predictors of clearance and volume of distribution, respectively. A statistical significant difference in the PK parameters between ethnic groups could not be identified. Simulations using PK/PD models showed that CYP2C9 genotype is the factor that affects the PDs of meloxicam. The genetic polymorphisms highlighted in this study would be beneficial for conducting clinical trials in East Asians with similar genetic backgrounds.

show abstract

Section: Study Highlightsmentioning

confidence: 99%

Section: Data Sourcementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The Role of Ethnicity on Drug Response

Aoyama

Ishida

Kaneko

et al. 2017

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

show abstract

“…Clinically significant inter-ethnic differences in drug response and pharmacokinetics have been reported for a number of drugs6,7. Differences in drug response may be attributable to differences in average pharmacokinetics and pharmacodynamics and in turn variations in drug safety and efficacy between populations have been reported.…”

Section: Introductionmentioning

confidence: 99%

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Yamada

Akita

Nakagawa

et al. 2013

Journal of Drug Assessment

View full text Add to dashboard Cite

ObjectivesBelimumab, an anti-B lymphocyte stimulator (BLyS) human monoclonal antibody, was approved in the United States, Canada and European Union for the treatment of the patients with systemic lupus erythematosus (SLE). However, belimumab had not been evaluated in Japanese patients. The objectives of this study were to evaluate the safety and tolerability of belimumab in Japanese patients with SLE, as well as to investigate the pharmacokinetics (PK) and biological activity of belimumab in this population.MethodsA total of 12 Japanese patients were enrolled in a randomized, single-blind, placebo-controlled, dose-ascending design study. A dosing regimen of a single intravenous infusion over 1 hour of belimumab (1 mg/kg and 10 mg/kg) was employed. Patients were followed for 84 days after dosing to assess adverse events, pharmacokinetics, biomarkers and SLE disease activity.Clinical trial registration numberClinicalTrials.gov identifier is NCT01381536.ResultsBelimumab (1 mg/kg and 10 mg/kg) demonstrated a favorable clinical safety and tolerability profile in Japanese patients with SLE. The incidence of adverse events was similar among the two belimumab groups and placebo group. The PK profile of single-dose belimumab was approximately dose proportional, and the long terminal elimination half-life (12.4–15.7 days), low clearance (3.55–4.65 mL/day/kg), and small volume of distribution (76.2–80.1 mL/kg) were consistent with a fully humanized antibody. Effects of belimumab on B cells suggested biological activity effects expected as an inhibitor of BLyS.LimitationThe small sample size and single dose design of this study prevent definitive conclusions regarding the safety, pharmacokinetics or pharmacodynamics of belimumab in a Japanese population being made.ConclusionsThe preliminary safety, PK profile, and observed biological activity of belimumab support further evaluation of its safety and efficacy in Japanese patient with SLE.

show abstract

“…2,4 Given that nmDMD is present in all ethnic groups, it is important to evaluate the possible effect of ethnic background on ataluren PK; differences in PK and PD among various ethnic groups are critical factors for understanding intersubject variability of a therapeutic agent. 22,32 The primary objective of this study was to investigate the PK of ataluren in healthy Japanese and Caucasian subjects. Additionally, ethnic extrinsic factors associated with environment, culture (such as diet), climate, medical practice, socioeconomic status, drug compliance, dosage regimen, and route of administration may also affect the PK and PD differences observed in various ethnic populations.…”

mentioning

confidence: 99%

Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects

Kong

Laskin

Kaushik

et al. 2019

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

To evaluate the potential for ethnicity‐related differences in ataluren pharmacokinetics (PK) and safety, a phase 1 single‐dose study was conducted in 48 healthy (24 Japanese and 24 Caucasian subjects), nonsmoking male volunteers who were equally divided into 3 cohorts of oral doses at 5, 10, and 20 mg/kg. Blood samples were collected until 48 hours postdose. PK results demonstrated rapid absorption of ataluren, with peak plasma levels (C max ) being attained between 0.875 and 2.5 hours after dosing. The mean C max and area under the concentration‐time curve (AUC (0‐last) ) increased with each increasing dose level in both Japanese and Caucasian subjects. Although the C max was similar across all subjects at each dose regardless of ethnicity, Japanese subjects had a mean AUC (0‐last) approximately 14% to 34% lower than that of Caucasian subjects across the 3 dose levels. This difference was likely due to the higher variability of AUC values in Caucasian subjects and the relatively small study population. In conclusion, similar ataluren PK profiles were observed in healthy Japanese and Caucasian subjects following single oral administration of ataluren at all dose levels.

show abstract

Ethnic Differences in Pharmacokinetics in New Drug Applications and Approved Doses in Japan

Cited by 22 publications

References 6 publications

Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The Role of Ethnicity on Drug Response

Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The Role of Ethnicity on Drug Response

Safety, tolerability, pharmacokinetics and pharmacodynamics of belimumab in Japanese patients with mild-to-moderate systemic lupus erythematosus

Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects

Contact Info

Product

Resources

About