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Urinary excretion of l-carnitine and its short-chain acetyl-l-carnitine in patients undergoing carboplatin treatment

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Abstract

Purpose

To evaluate the effect of the anti-cancer drug carboplatin on plasma concentrations and urinary excretion of l -carnitine (LC) and its main ester, acetyl-l-carnitine (ALC), in cancer patients.

Methods

Plasma and urine concentrations of LC and ALC from 11 patients on carboplatin therapy (1 h intravenous infusion; AUC dose 4.8 ± 1.1 mg/ml min) in combination with docetaxel, paclitaxel or vinorelbine, were determined by high-performance liquid chromatography with fluorimetric detection.

Results

Before carboplatin therapy, the mean ± SD plasma concentrations of LC and ALC were 47.8 ± 10.9 and 7.04 ± 1.04 nmoles/ml, respectively, and remained constant throughout the entire study period. In contrast, urinary excretion of LC and ALC, increased significantly during the chemotherapy from 115 ± 105 to 480 ± 348 μmoles/day (P < 0.01) and from 41 ± 41 to 89 ± 52 μmoles/day (P < 0.05) for LC and ALC, respectively, subsequently reverting to normal 6 days after the end of chemotherapy. Similarly, the renal clearance of LC and ALC increased substantially during chemotherapy from 1.67 ± 1.43 to 9.05 ± 9.52 ml/min (P < 0.05) and from 4.02 ± 4.51 to 7.97 ± 5.05 ml/min (P = not significant) for LC and ALC, respectively, reverting to normal 6 days after the end of chemotherapy. Plasma concentrations and urinary excretion of glucose, phosphate and urea nitrogen and creatinine clearance, however, were not affected by carboplatin therapy, indicating no impaired kidney function.

Conclusion

Treatment with carboplatin was associated with a marked urinary loss of LC and ALC, most likely due to inhibition of carnitine reabsorption in the kidney.

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Acknowledgments

This study was supported financially by Sigma-Tau SpA, Pomezia (Rome), Italy. The authors are grateful to the patients for donation of blood and urine samples. They also wish to thank Professor AM Evans for his critical review of the paper.

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Authors and Affiliations

  1. Scientific Department, Sigma-Tau, Via Pontina Km 30,400, Pomezia, Italy

    Angelo Mancinelli, S. D’Iddio & M. Calvani

  2. Medical Oncology Unit, Hospital of Fermo, Fermo, Italy

    R. Bisonni

  3. Medical Oncology Unit, Hospital of Urbino, Urbino, Italy

    F. Graziano

  4. Medical Oncology Unit, Hospital of Fano, Fano, Italy

    P. Lippe

Authors
  1. Angelo Mancinelli
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  2. S. D’Iddio
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  3. R. Bisonni
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  4. F. Graziano
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  6. M. Calvani
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Correspondence to Angelo Mancinelli.

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Mancinelli, A., D’Iddio, S., Bisonni, R. et al. Urinary excretion of l-carnitine and its short-chain acetyl-l-carnitine in patients undergoing carboplatin treatment. Cancer Chemother Pharmacol 60, 19–26 (2007). https://doi.org/10.1007/s00280-006-0341-3

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  • DOI: https://doi.org/10.1007/s00280-006-0341-3

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