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The effects of cimetidine upon the plasma pharmacokinetics of doxorubicin in rabbits

  • Original Articles
  • Cimetidine, Doxorubicin, Pharmacokinetics
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Summary

Cimetidine is an H2 antagonist which inhibits cytochrome P-450 and reduces hepatic blood flow. To determine whether cimetidine interferes with the plasma pharmacokinetics of doxorubicin, we gave six female New Zealand rabbits doxorubicin 3 mg/kg, followed a month later by cimetidine 120 mg/kg every 12 h over 72 h and doxorubicin 3 mg/kg. Serial plasma specimens were obtained over 72 h and assayed for doxorubicin and its metabolites by high-performance liquid chromatography and fluorescence detection.

Doxorubicin plasma pharmacokinetics were prolonged after cimetidine pretreatment [AUC 0.76±0.22 vs. 2.85±1.22 μM×h, no pretreatment vs pretreatment (p=0.005), half-life=11.7±6.55 vs 28.0±8.16 h (P=0.0002), and clearance=0.129±0.036 vs 0.036±0.0111/min-1 kg-1 (P=0.0007)]. No significant differences were found between the AUCs for doxorubicinol, 7-deoxy doxorubicinol aglycone, or two unidentified nonpolar metabolites in nonpretreatment and pretreatment studies. Cimetidine increases and prolongs the plasma exposure to doxorubicin in rabbits. Doxorubicin metabolism does not appear to be affected by cimetidine.

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Authors and Affiliations

  1. Department of Medicine, The Nashville Veterans Administration Medical Center, 37203, Nashville, TN, USA

    Dean E. Brenner, Jerry C. Collins & Kenneth R. Hande

  2. Vanderbilt University, 37203, Nashville, TN, USA

    Dean E. Brenner, Jerry C. Collins & Kenneth R. Hande

  3. Department of Clinical Pharmacology and Experimental Therapeutics, Roswell Park Memorial Institute, 666 Elm Street, 14263, Buffalo, NY, USA

    Dean E. Brenner

Authors
  1. Dean E. Brenner
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  2. Jerry C. Collins
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  3. Kenneth R. Hande
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Additional information

Grant Support Veterans Administration, NIH Grant RR-05424 and Clinical Research Center Grant RR-00095 American Cancer Society Institutional Grants #IN25V and IN24V, and JFCF #649

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Brenner, D.E., Collins, J.C. & Hande, K.R. The effects of cimetidine upon the plasma pharmacokinetics of doxorubicin in rabbits. Cancer Chemother. Pharmacol. 18, 219–222 (1986). https://doi.org/10.1007/BF00273389

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  • DOI: https://doi.org/10.1007/BF00273389

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