Interaction of cimetidine but not ranitidine with cyclophosphamide in mice

Research output: Contribution to journalArticle

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Abstract

A series of experiments in DBA/2J mice evaluated the biological and pharmacokinetic interactions of the alkylating agent cyclophosphamide (CTX) and the histamine-H2 antagonists cimetidine (CMT) and ranitidine (RNT). Doses were adjusted to approximate human dose levels: 100 mg/kg for CMT; and 25 mg/kg for RNT. CMT reduced the survival of normal (bone marrow stem cell) colony forming units in a dose dependent fashion. CMT, given 5 or 30 min before CTX (200 mg/kg), significantly increased the survival of leukemia bearing mice, as well as the elimination half-life and plasma area under the curve of total alkylating metabolites of CTX. RNT did not significantly alter CTX antileukemic activity, pharmacokinetics, or toxicity to normal bone marrow stem cells. These results suggest caution in the use of CMT in patients being treated with CTX in order to avoid the possibility of exaggerated CTX toxicities. RNT may comprise a safer histamine-H2 antagonist to use with CTX if a histamine-H2 antagonist is clinically indicated.

Original languageEnglish (US)
Pages (from-to)1795-1799
Number of pages5
JournalCancer Research
Volume46
Issue number4
StatePublished - 1986

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Ranitidine
Cimetidine
Cyclophosphamide
Histamine H2 Antagonists
Stem Cells
Bone Marrow Cells
Pharmacokinetics
Inbred DBA Mouse
Survival
Alkylating Agents
Area Under Curve
Half-Life
Leukemia

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Interaction of cimetidine but not ranitidine with cyclophosphamide in mice. / Dorr, Robert T; Alberts, David S; Alberts, D. S.

In: Cancer Research, Vol. 46, No. 4, 1986, p. 1795-1799.

Research output: Contribution to journalArticle

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