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Pharmacokinetics

Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation

Bone Marrow Transplantation volume 28, pages 821–825 (2001)Cite this article

Abstract

Busulfan pharmacokinetic parameters are useful in predicting the outcome of allogeneic bone marrow transplantation (BMT). Standard pharmacokinetic measurements require multiple blood samples. Various limited sampling models (LSM) have been proposed for reducing the sample number required for these measurements, essentially for patients with malignant disorders undergoing BMT. This study was undertaken to evaluate the existing LSM for busulfan pharmacokinetics to find out the most suitable method for patients with thalassaemia major undergoing BMT. Busulfan levels in plasma samples were analysed by HPLC. The AUC calculated by non-compartmental analysis using the program ‘TOPFIT’ was compared with previously published LSMs. Our seven sample pharmacokinetic data for AUC calculation was compared with the published LSMs. The three sample models suggested by Chattergoon et al and Schuler et al showed significant agreement with AUC TOPFIT (R2 = 0.98 and 0.94, respectively) in our clinical context. Other models resulted in significant over or under representation of observed values (Vassal's model R2 = 0.61; Chattergoon's two sample model R2 = 0.84; four sample model R2 = 0.83; Schuler's two sample model R2 = 0.79). By these data the three sample LSM proposed by Chattergoon et al and Schuler et al are suitable for calculation of the AUC in patients with thalassaemia major undergoing BMT conditioned with oral busulfan. Bone Marrow Transplantation (2001) 28, 821–825.

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Acknowledgements

This study was supported in part by the Indo–French center for the promotion of advanced research (IFCPAR): project No. 2403–2. We also thank Ms Claudine Brunner for her help in preparing the manuscript.

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Authors and Affiliations

  1. Department of Haematology, Christian Medical College and Hospital, Vellore, India

    P Balasubramanian, M Chandy & A Srivastava

  2. INSERM U 458, Hopital Robert Debre, Paris, France

    R Krishnamoorthy

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  1. P Balasubramanian
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  2. M Chandy
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  3. R Krishnamoorthy
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  4. A Srivastava
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Balasubramanian, P., Chandy, M., Krishnamoorthy, R. et al. Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation. Bone Marrow Transplant 28, 821–825 (2001). https://doi.org/10.1038/sj.bmt.1703245

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