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Racial difference in bioavailability of oral ibandronate between Caucasian and Taiwanese postmenopausal women

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Abstract

Summary

Following 150 mg of oral ibandronate, Taiwanese females have greater serum and urine levels of this drug and bone resorption marker suppression than Caucasian women. These inter-ethnic differences seems to be partly explained by a 2.48-fold higher bioavailability of ibandronate in Taiwanese postmenopausal women.

Introduction

Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women.

Methods

Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F).

Results

The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables.

Conclusions

Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity

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Acknowledgments

We are grateful to Ms Shu-Chen Chung for her assistance in data request and Professor Yung-jin Lee for his valuable comment on R-based tools for pharmacokinetic modeling.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    W.-Y. Chiu, W.-S. Yang & K.-S. Tsai

  2. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, No. 7, Chung Shan South Road, Zhongzheng Dist, Taipei, 10002, Taiwan

    W.-Y. Chiu & W.-S. Yang

  3. Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung Shan South Road, Zhongzheng Dist, Taipei, 10002, Taiwan

    W.-Y. Chiu & K.-S. Tsai

  4. School of Pharmacy, National Taiwan University, Taipei, Taiwan

    C.-J. Lin

  5. Department of Public Health, Epidemiology and Health Economics, University of Liège, Quartier Hôpital, CHU B23, Avenue Hippocrate, 13, 4000, Liege, Belgium

    J.-Y. Reginster

  6. Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia

    J.-Y. Reginster

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  1. W.-Y. Chiu
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Correspondence to W.-S. Yang, K.-S. Tsai or J.-Y. Reginster.

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This work was authorized and supported by F. Hoffmann-La Roche Ltd. (Basel, Switzerland). The views and conclusions contained herein are those of the authors and do not represent those of F. Hoffmann-La Roche Ltd.

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Chiu, WY., Lin, CJ., Yang, WS. et al. Racial difference in bioavailability of oral ibandronate between Caucasian and Taiwanese postmenopausal women. Osteoporos Int 31, 193–201 (2020). https://doi.org/10.1007/s00198-019-05127-y

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