Tuesday, 1 December 2015

verapamil and TMZ

Stephen,
. IF I was to take verapamil with temodal do I need to start the verapamil a few days before starting temodal also if that is correct and once that is established can I take both drugs at the same time? Would it effect the absorption of temodal? I wanted to take them so they are both in the system at peak plasma times. From what I've read the  time to peak plasma concentration for temodal is 1 hour, half life 1.8 and Verapamil immediate release is 1 - 2 hours for  and half life is 2.8 to 7.4 hours Verapamil extended release with food is 12hours to peak plasma concentration and without food 7 hours. as per link below.

I have both immediate release and slow release but not sure how Alan will respond so not sure if we'll end up taking the SR or the immediate release. Do you know what the best time frame to maximise  Verapamil's multidrug resistance effect along with Temodal for both slow release and immediate release would be.
http://www.medsafe.govt.nz/profs/datasheet/v/VerpamilSRtab.pdf

2 comments:

  1. I'm not aware of any deleterious interaction between verapamil and TMZ. If anything, verapamil would improve the absorption of TMZ through P-glycoprotein inhibition in the intestines. However TMZ is probably not a major P-gp substrate so it might make little difference to absorption.

    In terms of chemosensitizing, there may be other mechanisms for verapamil beyond P-gp inhibition.

    Ben took verapamil for the week surrounding the CCNU or BCNU, that is, for a few days before and after chemo. I don't have any strong opinion on this.

    In general, immediate release drugs give a more dramatic plasma spike and decline with a higher Cmax, while extended release gives a more sustained plasma concentration, with a lower Cmax.

    There was a clinical trial done with verapamil in combination with chemo for advanced non-small cell lung cancer. Verapamil was started 24 hours prior to the chemo. It was given at 160 mg three times daily. Survival was better in the verapamil + chemo arm.

    http://www.ncbi.nlm.nih.gov/pubmed/8388231

    You can find in vitro studies showing verapamil increases sensitivity to TMZ, but I have seen no animal or human studies on this.

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  2. Thanks Stephen, very much appreciated,

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