Cargando…

Cimetidine enhancement of cyclophosphamide antitumour activity.

Male DBA2 mice were given 10(6) P-388 leukaemic cells i.p. and cimetidine (CMT) at 100 mg/kg 1 day for 10 days, or as a single 100 mg/kg injection 30 min before cyclophosphamide (CTX). CMT significantly prolonged the survival of groups of mice receiving 50, 100 and 200 mg/kg of CTX 3 days after tumo...

Descripción completa

Detalles Bibliográficos
Autores principales: Dorr, R. T., Alberts, D. S.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1982
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2010952/
https://www.ncbi.nlm.nih.gov/pubmed/7059463
_version_ 1782136430202454016
author Dorr, R. T.
Alberts, D. S.
author_facet Dorr, R. T.
Alberts, D. S.
author_sort Dorr, R. T.
collection PubMed
description Male DBA2 mice were given 10(6) P-388 leukaemic cells i.p. and cimetidine (CMT) at 100 mg/kg 1 day for 10 days, or as a single 100 mg/kg injection 30 min before cyclophosphamide (CTX). CMT significantly prolonged the survival of groups of mice receiving 50, 100 and 200 mg/kg of CTX 3 days after tumour inoculation. Median survival increased by 5.5 days (P less than 0.05), 10 days (P less than 0.05) and 13 days (P less than 0.05) respectively. The addition of CMT had the effect of roughly doubling the CTX dose, without increasing the lethality. CMT produced the only long-term survival seen in the study (1-2/10) CMT alone had no apparent antitumour activity. CMT significantly prolonged mean pentobarbital sleep to 28.6-60 min vs only 10 min for phenobarbital treated mice. Both CMT regimens increased the plasma concentration time products for CTX-induced metabolites (NBP) by about 1.3 fold (in contrast to a 33% reduction with phenobarbital). On average the single-dose CMT regimen produced the greatest effect on survival, on pentobarbital sleep duration and on total NBP reactive species. Probable mechanisms for the CMT-CTX interaction include competitive microsomal enzyme inhibition and/or acutely depressed hepatic blood flow. Caution should be used in combining CMT with full doses of CTX and any other highly metabolized antineoplastic agents in man.
format Text
id pubmed-2010952
institution National Center for Biotechnology Information
language English
publishDate 1982
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-20109522009-09-10 Cimetidine enhancement of cyclophosphamide antitumour activity. Dorr, R. T. Alberts, D. S. Br J Cancer Research Article Male DBA2 mice were given 10(6) P-388 leukaemic cells i.p. and cimetidine (CMT) at 100 mg/kg 1 day for 10 days, or as a single 100 mg/kg injection 30 min before cyclophosphamide (CTX). CMT significantly prolonged the survival of groups of mice receiving 50, 100 and 200 mg/kg of CTX 3 days after tumour inoculation. Median survival increased by 5.5 days (P less than 0.05), 10 days (P less than 0.05) and 13 days (P less than 0.05) respectively. The addition of CMT had the effect of roughly doubling the CTX dose, without increasing the lethality. CMT produced the only long-term survival seen in the study (1-2/10) CMT alone had no apparent antitumour activity. CMT significantly prolonged mean pentobarbital sleep to 28.6-60 min vs only 10 min for phenobarbital treated mice. Both CMT regimens increased the plasma concentration time products for CTX-induced metabolites (NBP) by about 1.3 fold (in contrast to a 33% reduction with phenobarbital). On average the single-dose CMT regimen produced the greatest effect on survival, on pentobarbital sleep duration and on total NBP reactive species. Probable mechanisms for the CMT-CTX interaction include competitive microsomal enzyme inhibition and/or acutely depressed hepatic blood flow. Caution should be used in combining CMT with full doses of CTX and any other highly metabolized antineoplastic agents in man. Nature Publishing Group 1982-01 /pmc/articles/PMC2010952/ /pubmed/7059463 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Dorr, R. T.
Alberts, D. S.
Cimetidine enhancement of cyclophosphamide antitumour activity.
title Cimetidine enhancement of cyclophosphamide antitumour activity.
title_full Cimetidine enhancement of cyclophosphamide antitumour activity.
title_fullStr Cimetidine enhancement of cyclophosphamide antitumour activity.
title_full_unstemmed Cimetidine enhancement of cyclophosphamide antitumour activity.
title_short Cimetidine enhancement of cyclophosphamide antitumour activity.
title_sort cimetidine enhancement of cyclophosphamide antitumour activity.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2010952/
https://www.ncbi.nlm.nih.gov/pubmed/7059463
work_keys_str_mv AT dorrrt cimetidineenhancementofcyclophosphamideantitumouractivity
AT albertsds cimetidineenhancementofcyclophosphamideantitumouractivity