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Early pharmacokinetics of low dosage mycophenolate exposure in Thai kidney transplant recipients

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Abstract

Background The effects of mycophenolic acid exposure in the early period after transplantation on clinical outcomes have been reported; however, mycophenolic acid exposure in the early period after transplantation in Asian kidney transplant recipients who receive 1.5 g/d mycophenolate mofetil has never been investigated. Objective To determine mycophenolic acid exposure on day 3 post-transplantation in kidney transplant recipiens who receive 1.5 g/d mycophenolate mofetil. The effects of the reduced renal function on mycophenolic acid area under the concentration–time curve (AUC) and the achievement of the target AUC on the incidence of biopsy proven acute rejection during the first month post-transplantation were also evaluated. Setting A university hospital Method Blood samples and 24-h urine were collected on day 3 post-transplantation. Main outcome measures The mycophenolic acid AUC was calculated by linear trapezoidal rule and compared with the target of 45 mg*h/L. Results Of 42 Thai kidney transplant recipiens, the mean mycophenolic acid AUC of 45.1 mg*h/L (SD 14.7) was comparable to the AUC target (P = 0.962). Significant differences of the mycophenolic acid AUC were observed between patients with urine output of < 2400 mL and those with urine output ≥ 2400 mL (35.3 ± 6.6 and 47.4 ± 15.2, respectively; P = 0.002), and between patients with 24-h measured CrCl < 25 mL/min and those with CrCl ≥ 25 mL/min (38.0 (29.0, 42.2) and 49.2 ± 14.0, respectively; P = 0.017). Proportions of overall biopsy proven acute rejection among patients with mycophenolic acid AUC of < 45 and ≥ 45 mg*h/L were comparable (20.0% and 23.5%, respectively; P = 1.000). Conclusions After the starting dosage of 1.5 g/d mycophenolate mofetil, the mean mycophenolic acid AUC on day 3 post-kidney transplantation is comparable with the target of 45 mg*h/L. Severely reduced renal function significantly influences mycophenolic acid exposure.

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Acknowledgements

The authors would like to thank Dr.Thidarat Kitrungphaiboon, Dr.Suwasin Udomkarnjananun, Dr.Natavudh Townamchai, Ms.Manorom Poosoonthornsri, Mr.Pheeraphat Sarppreuttikun and the staffs of King Chulalongkorn Memorial Hospital for their helps.

Funding

This research received full financial support from the Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand (Grant number: Phar2560-RG06 to Somratai Vadcharavivad).

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Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Busaya Kulabusaya & Somratai Vadcharavivad

  2. Pharmacy Department, Siriraj Hospital, Bangkok, 10700, Thailand

    Busaya Kulabusaya

  3. Department of Medicine, Renal Immunology and Therapeutic Apheresis Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Yingyos Avihingsanon

  4. Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands

    Teun van Gelder

  5. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    Teun van Gelder

  6. Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Kearkiat Praditpornsilpa

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  1. Busaya Kulabusaya
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Correspondence to Somratai Vadcharavivad.

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Conflicts of interest

Yingyos Avihingsanon received research support from Astellas Pharmaceuticals. Teun van Gelder has received lecture fees from Roche, Chiesi and Astellas Pharma, research support from Chiesi and Astellas, and consulting fees from Astellas, Novartis and Roche Diagnostics. The other authors declare no conflict of interest related to this work.

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Kulabusaya, B., Vadcharavivad, S., Avihingsanon, Y. et al. Early pharmacokinetics of low dosage mycophenolate exposure in Thai kidney transplant recipients. Int J Clin Pharm 41, 1047–1055 (2019). https://doi.org/10.1007/s11096-019-00848-w

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