Is This the Drug or Dose for You?: Impact and Consideration of Ethnic Factors in Global Drug Development, Regulatory Review, and Clinical Practice

Huang, Suli; Temple, Robert

doi:10.1038/clpt.2008.144

Cited by 141 publications

(126 citation statements)

References 16 publications

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“…In the CHAMP study, most participants were of Australian (49.8%) or Italian (19.6%) descent [13]. Ethnic differences have been observed with African-Americans having a denser lean body mass than Whites [28] and in the pharmacokinetics and pharmacodynamic responses of Asians to different drugs [29], and it is possible that this may also be a factor in the measurement of LBW and FFM, although further studies need to investigate this.…”

Section: Discussionmentioning

confidence: 99%

Estimation of lean body weight in older community‐dwelling men

Mitchell

Kirkpatrick

Couteur

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?• Lean mass decreases with age while total body fat increases, leading to changes in the pharmacokinetics and pharmacodynamics of drugs.• Dual-energy X-ray absorptiometry (DXA) is a useful reference method to measure lean body weight but may not be readily utilized clinically.• Limited methods for measurement of lean body weight using easily obtainable participant characteristics, such as height and weight, have been validated for use in people aged Ն65 years. WHAT THIS STUDY ADDS• This study has shown that lean body weight can be estimated using three different equations from easily obtainable participant characteristics with results comparable to DXA-derived estimates.• These equations may be useful tools to estimate lean body weight in situations where DXA is not practical. AIMSLean body weight (LBW) decreases with age while total body fat increases, altering drug pharmacokinetics. The aim of this study was to evaluate the ability of the LBW equation to predict dual-energy X-ray absorptiometry (DXA)-derived fat free mass (FFMDXA) in older community-dwelling males compared with that of two existing FFM equations: the Heitmann and Deurenberg equations. METHODSData were obtained from 1655 older men enrolled in the Concord Health and Ageing in Men Project. The predictive performance of the LBW and FFM equations to predict FFMDXA accurately was assessed graphically using Bland-Altman plots and quantitatively for precision and bias using the method of Sheiner and Beal in all participants and in frailty and body mass index (BMI) subgroups. RESULTSThe LBW and Heitmann equations consistently overestimated FFMDXA for all frailty and BMI subgroups with a mean difference [95% confidence interval (CI)] of 5.5 kg (-0.65, 11.63 kg) and 3.34 kg (-2.84, 9.64 kg), respectively. The Deurenberg equation overestimated FFMDXA for overweight participants but underestimated FFMDXA for not-frail participants, with a mean difference (95% CI) of 1 kg (-7.23, 5.25 kg) for all participants. CONCLUSIONLBW and FFM estimated using these equations give results comparable to DXA-derived FFM. The LBW and Heitmann equations provide a more consistent estimate of FFMDXA in all frailty and BMI groups despite the Deurenberg equation having the smallest mean difference. Further studies to determine whether the LBW equation is a clinically useful substitute for weight when determining drug dose in older people appear warranted.

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Section: Discussionmentioning

confidence: 99%

Estimation of lean body weight in older community‐dwelling men

Mitchell

Kirkpatrick

Couteur

et al. 2010

Brit J Clinical Pharma

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“…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

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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.

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“…Geographic region is becoming increasingly recognized as an important factor accounting for variation in drug response (Huang and Temple, 2008;O'Donnell and Dolan, 2009). For example, there is consistent evidence that persons from East Asia are particularly sensitive to the effects of platinating agents (Millward et al, 2003;Watanabe et al, 2003).…”

Section: Population Of Persons From Whom Cells Are Derivedmentioning

confidence: 99%