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Pharmacokinetic Study of Saxagliptin in Healthy Chinese Subjects

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Abstract

Background and Objectives: The pharmacokinetics of some medications may be affected by differences in race and ethnicity, which can lead to suboptimal outcomes. The present study was conducted to assess the single- and multiple-dose pharmacokinetics of saxagliptin in healthy Chinese subjects living in China.

Methods: This was an open-label, 9-day study conducted at the Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China. Sixteen healthy Chinese subjects of both sexes between 21 and 33 years of age were administered saxagliptin 5mg orally on day 1, then once daily on days 3–7. Pharmacokinetic variables for saxagliptin (primary outcome) and its active metabolite, 5-hydroxy saxagliptin (secondary outcome), after single and multiple oral doses of saxagliptin were assessed. Safety was also assessed.

Results: Saxagliptin was absorbed rapidly (median time to reach maximum concentration [tmax]: 0.5 and 1 hour on days 1 and 7, respectively), and its pharmacologically active metabolite, 5-hydroxy saxagliptin, appeared in plasma (median tmax: 1.0 and 1.5 hours, respectively). Plasma exposure to 5-hydroxy saxagliptin was approximately 2- to 3-fold higher than exposure to saxagliptin. Plasma concentration-time profiles for saxagliptin and 5-hydroxy saxagliptin were similar on days 1 and 7, with no evidence of drug accumulation on repeated dosing. The elimination half-lives (t1/2) for saxagliptin and 5-hydroxy saxagliptin were approximately 3 and 4 hours, respectively, with renal excretion as the primary route of elimination. After single and multiple dosing, 54.48% and 52.60%, respectively, of the administered saxagliptin dose was recovered in urine as unchanged drug or 5-hydroxy saxagliptin. Saxagliptin was generally well tolerated. Six (37.5%) subjects experienced an adverse event (AE). All AEs were mild in intensity and judged by the investigator as not related to the study medication. There were no deaths, serious AEs, discontinuations due to AEs, or other clinically significant AEs during this study.

Conclusion: Saxagliptin 5 mg (single dose and once-daily doses for 5 days) was generally well tolerated; the pharmacokinetics of saxagliptin and 5-hydroxy saxagliptin in healthy Chinese subjects were consistent with previous assessments in the saxagliptin clinical development program.

Trial Registration: ClinicalTrials.gov identifier: NCT00770302.

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Acknowledgements

The authors gratefully acknowledge the staff of the Phase I Unit at Peking University Third Hospital in Beijing, China, including Dr Zhenhua Yang for medical assistance, Yifang Zhang, head nurse, for medical support and unit management, and Shuang Zhang for medical assistance. Chemical analysis was conducted by WuXi AppTec, Shanghai, China. Medical writing and editorial assistance with language, consistency of style, and general editing services for this manuscript was provided by Paul Ruest, PhD, and Jessica Uychich, Quintiles Medical Communications, Parsippany, NJ, USA.

Publication support for this manuscript was provided by AstraZeneca and Bristol-Myers Squibb. AstraZeneca and Bristol-Myers Squibb designed and sponsored the current study. June Zhao was involved in design of the study. All of the authors contributed to the conduct, data analysis/interpretation, and independently drafted, critically revised and approved the final manuscript.

Haiyan Li and Li Yang are employees of Peking University Third Hospital. Conrad Tou and June Zhao are employees of AstraZeneca. Chirag Patel was an employee of Bristol-Myers Squibb at the time this study was conducted and the manuscript was written and initially submitted for publication. None of the authors have anything further to disclose.

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Authors and Affiliations

  1. Department of Cardiology and Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China

    Haiyan Li

  2. Department of Pharmacy, Peking University Third Hospital, Beijing, China

    Li Yang

  3. Biostatistics and Informatics, AstraZeneca, Wilmington, Delaware, USA

    Conrad K. P. Tou

  4. Cardiovascular & Metabolic Diseases, Discovery Medicine & Clinical Pharmacology, Bristol-Myers Squibb R&D, Princeton, New Jersey, USA

    Chirag G. Patel

  5. Strategic Development, AstraZeneca, 1800 Concord Pike, Wilmington, Delaware, DE 19850, USA

    June Zhao MD, PhD

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  1. Haiyan Li
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  2. Li Yang
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  4. Chirag G. Patel
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  5. June Zhao MD, PhD
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Correspondence to June Zhao MD, PhD.

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Li, H., Yang, L., Tou, C.K.P. et al. Pharmacokinetic Study of Saxagliptin in Healthy Chinese Subjects. Clin Drug Investig 32, 465–473 (2012). https://doi.org/10.2165/11598760-000000000-00000

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