Wednesday, April 24, 2019

Therapeutic drug monitoring intro

It has become a standard format in therapeutic drug monitoring recommendation in Malaysia where we will inform:
  • the drug level, and is it subtherapeutic or in toxic range
  • withold or continue the drug based on drug level and pharmacokinetics calculation, and finally
  • recommendations on standard monitoring parameter.
Well, it is a systematic recommendation but it is never that simple and sweet.

There is a few fundamental concepts that we should understand. First, managing a patient, it is never based solely on therapeutic drug level. It is not always when the drug is lower than reference range, then we increase the dose and vice versa. We should take into account patient clinical progress.

In fact, to give a justified and correct recommendation, we should have a background knowledge on the clinical conditions that we are discussing at. To illustrate, before we start to discuss phenytoin drug level adjustment, we should have a basic understanding on what is meant by epilepsy and what is the first line management for each sub-types. Do you know that carbamazepine should not be given to manage absence seizure? If the drug is not indicated, therapeutic drug monitoring would not be needed.

Next, we should have a clear understanding of why we do TDM and the occasions when we do it. For simplistic purpose, I hereby listed down three different occasions where we do a TDM:
  • First, it is to ensure the narrow therapeutic window drug level is within therapeutic range. If the drug level is below or above the range, it will serve as a guide for dosage adjustment. However, the result should be interpreted in a clinical context. To illustrate, we would not adjust the dose of antiepileptic drug if the patient is seizure free despite has a drug level lower than therapeutic range.
  • to check patient compliance to a drug, for example when we do a random sampling of an antiepileptic.
  • to check for drug toxicity if suspected, for example paracetamol poisoning.
In TDM, we will use population pharmacokinetics developed by researches to do a drug estimation. However, every one of us is very different from each other, including how our body react to an administered drug. Scientifically speaking, there could be an interpatient variability in the dose-concentration relationship or what we termed as "pharmacokinetic difference”. It is only after doing a TDM, we might be able to draw out a more precise estimation based on the individual patient profile. In real practice, the estimated value does not equivalent to the actual measured value. Hence, resampling of drug is often unavoidable.

I have seen times that we used a wrong formula, a wrong estimation will be produced from the standard formula. Then, it is followed by wrong recommendations. Hence, not to forget, formulas are like our computer software, it only does what they are being tasked for. It will be garbage in, garbage out. Hence, hopefully, an appreciation should be given to the TDM formulae, instead of blindly using them.

See you in the next discussion.

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