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Influence of hydration on ultrafilterable platinum kinetics and kidney function in patients treated withcis-diamminedichloroplatinum(II)

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Summary

It has been reported that hypertonic saline provides protection against the renal toxicity of cisplatin (CDDP). We therefore evaluated its influence on the plasma and urinary pharmacokinetics of ultrafilterable platinum and kidney function as estimated by creatinine, inulin and PAH clearance. We undertook a randomized trial including two groups of ten patients receiving 100 mg/m2 CDDP in isotonic (group 1) or hypertonic saline (group 2) by a 20-min infusion. The hydration consisted of dextrose in group 1 and isotonic saline in group 2. Maximal concentration (Cmax), protein binding and cumulative urinary excretion were significantly higher in the dextrose group. Urinary flow decreased in this group but not in the other one. Inulin clearance was higher in the dextrose group than in the saline group andP-aminohippuric acid (PAH) clearance was not significantly different in these groups of patients. Hyponatremia was observed in the dextrose group. These results suggest that hypertonic saline infusion and saline hydration may enhance the diffusion of CDDP into tissues, lowering Cmax and renal excretion of platinum. The reduction of protein binding may indicate a diminution of aquation of CDDP in plasma. Our results suggest that the infusion of CDDP in hypertonic saline with salt hydration could exert a protective effect on the kidney. Moreover, there is a lessening of the risk of cellular hyperhydration. However, the better influence of dextrose hydration on glomerular filtration leads us to recommend a combination of the two methods of hydration for better tolerance and efficacy.

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Authors and Affiliations

  1. Département de Pharmacologie Clinique, Hopital Général, 3 rue du Faubourg Raines, F-21000, Dijon, France

    Monique Dumas, Viviane Chadoint-Noudeau & André Escousse

  2. Centre de Lutte contre le Cancer Georges François Leclerc, France

    Catherine de Gislain & Jacques Guerrin

  3. Departement d’Informatique Médicale, Hopital du Bocage, France

    Philippe d’Athis

  4. Laboratoire de Chimie Analytique, Faculté de Pharmacie, 21000, Dijon, France

    Nicole Autissier

Authors
  1. Monique Dumas
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  2. Catherine de Gislain
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  3. Philippe d’Athis
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  4. Viviane Chadoint-Noudeau
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  5. André Escousse
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  6. Jacques Guerrin
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  7. Nicole Autissier
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Dumas, M., de Gislain, C., d’Athis, P. et al. Influence of hydration on ultrafilterable platinum kinetics and kidney function in patients treated withcis-diamminedichloroplatinum(II). Cancer Chemother Pharmacol 26, 278–282 (1990). https://doi.org/10.1007/BF02897230

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  • DOI: https://doi.org/10.1007/BF02897230

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