Hi,

Please find FDA definitions of 'metabolite' below:

"Disproportionate drug metabolite — A metabolite present only in humans or present at higher plasma concentrations in humans than in the animals used in nonclinical studies. In general, these metabolites are of interest if they account for plasma levels greater than 10 percent of total drug-related exposure, measured as area under the curve at steady state.

Metabolite — A compound derived from the parent drug through phase 1 and/or phase 2 metabolic pathways.

Pharmacologically active metabolite — A metabolite that has pharmacological activity at the target receptor. The activity may be greater than, equal to, or less than that of the parent drug."

Source: https://www.fda.gov/media/72279/download

Based on the definition, 'degradation' is not a synonym for metabolism.

Best regards,

Tomasz

Tomasz Grabowski

Thank you for your detailed reply. I'd like to ask you another question.

If the drug (e.g. chloroquine) is co-incubated with RBC in vitro, and the RBC uptake 70% of the drug. Can this process be called 'drug metabolism inside RBC'?

I look forward to your professional reply.

Hi,

If the drug is 'distributed' to RBC its drug distribution is not metabolism. Word 'uptake' is not best to describe this process. It's rather part of the distribution. Please check the wording and content of the source below:

http://esteve.org/wp-content/uploads/2018/01/138200.pdf

..... but of course, in the effect the drug distribution, depending on its nature could be metabolized in RBC. So the context of distribution into the RBC could be more complex. Both processes are by definition separate but of course, the 'metabolism' of the drug in RBC will be dependent on its 'distribution' into the red blood cells compartment.

Please check the next source: Article Role of the red blood cell in drug metabolism

Best regards

Tomasz