I was at a conference last week where there were two very interesting presentations on monitoring drug levels in serum/plasma to aid understanding of effective dose rates. So-called Therapeutic Drug Monitoring (TDM) is useful where drugs are taken long term to prevent or minimise disease occurrence/recurrence. One paper related to monitoring levels in epilepsy patients to avoid seizures, the other was on TKIs.
Prof Bob Flanagan from Kings College Hospital presented on TKIs. New assay methods enables the plasma levels of both the TKI and its metabolite to be measured more readily (and at lower cost). This opens up TDM as tool in several areas
- assessing dose rates in children (some TKIs may limit growth, so dose needs to be minimum possible to be effective.)
- understanding why some patients do not respond to some TKIs (e.g. people who do not respond to Imatinib but do to other TKIs)
- understanding drug interactions, which may be important as current TKI patients grow old and develop other conditions
- establishing any links between serum levels and response, and maximising responsive while minimising side effects.
He presented some fascinating data which showed plasma level for patients on 400mg Imatinib varying from about 0.5mg/L to 5.0 mg/L. This a small level of correlation between increasing average serum level and improved response up to CMR/PCRU, but in the main this data (which is not a formal trial but gathered from just over 100 patients at a clinic) shows that MMR can be attained at what is the accepted level for theraptic effectiveness of 1mg/L.
He was unaware of the studies which have been listed on this web-site on people maintaining response after ceasing taking TKIs, so I have forwarded him the links. He was particularly interested in the study which showed that female patients were more likely to maintain response after ceasing TKI therapy, and is re-evaluating his data for sex of patient to see if there are any differences.
I have copied his conclusions slide below
TDM of TKIs may be beneficial in:
- Assessing adherence
- Ensuring adequate dosage (minimise selection of resistant clones)
- Minimising the risk/severity of toxicity (improve adherence hence outcome)
- Children/adolescents (maintain normal growth)
Need assays with:
- Minimal sample preparation
- Fast turn-around time
- Good accuracy, sensitivity, selectivity, measure plasma metabolites
I have sent Sandy abstracts of 3 papers he quoted to put on the web-site. Prof Flanagan is a very eminent toxicologist, and its great to see him engaged in this work.
