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Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients

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Abstract

Purpose

To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity.

Methods

TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3–16 years) and in 8 adults (mean age 30 years, range 19–54 years).

Results

In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ Cmax, t1/2, Vd or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not.

Conclusions

No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.

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Acknowledgements

This work was supported by AIRC, FOP and MURST.

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Authors and Affiliations

  1. Division of Pediatric Oncology, Department of Pediatrics, Catholic University, Largo A. Gemelli, 8, 00168, Rome, Italy

    Anna Riccardi, Giorgio Mazzarella, Vita Ridola, Antonio Ruggiero, Stefano Mastrangelo, Ilaria lazzareschi & Riccardo Riccardi

  2. Istituto Nazionale dei Tumori, Milan, Italy

    Graziella Cefalo & Maura Massimino

  3. Institute G. Gaslini, Genoa, Italy

    Maria Luisa Garrè

  4. Division of Oncology, Catholic University, Rome, Italy

    Carlo Barone

  5. University of Turin, Italy

    Alessandro Sandri & Enrico Madon

  6. Institute of Neurosurgery, Catholic University, Rome, Italy

    Massimo Caldarelli & Giulio Maira

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  1. Anna Riccardi
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  2. Giorgio Mazzarella
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  3. Graziella Cefalo
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  4. Maria Luisa Garrè
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  8. Vita Ridola
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  11. Ilaria lazzareschi
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  13. Giulio Maira
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  14. Enrico Madon
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  15. Riccardo Riccardi
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Correspondence to Riccardo Riccardi.

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Riccardi, A., Mazzarella, G., Cefalo, G. et al. Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients. Cancer Chemother Pharmacol 52, 459–464 (2003). https://doi.org/10.1007/s00280-003-0677-x

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  • DOI: https://doi.org/10.1007/s00280-003-0677-x

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