Calculating effective elimination half-life with active metabolites

[NeuroPsyence]

I think this concept will be easiest for me to understand through an example, so here's a hypothetical situation.

Substance D has an elimination half-life of 3 hours. It produces one metabolite, which has identical pharmacological activity, but an elimination half-life of 8 hours.

Can an effective half-life be calculated for the combined effects of the parent substance and its metabolite? Is it simply additive, or is the calculation more complex than that?

Thanks in advance for the information/explanation!

 

[sekio]

Is it simply additive, or is the calculation more complex than that?

It depends on the drug in question.

 

[NeuroPsyence]

It depends on the drug in question.

Doesn't metabolic elimination of nearly all drugs follow first-order kinetics? What other factors would be expected to influence the calculation?

 

[sekio]

I would think it would depend on the relative rates the metabolite is generated at, versus the excretion rate of the parent compound. If the prodrug is excreted before it can be broken down there will be less cumulative effects. Remember, elimination factors in both metabolism and e.g. urinary and fecal excretion.

Assuming that the majority of the drug is metabolised before it is excreted, and that the two compounds don't interact in any way (e.g. competing for plasma binding, or inhibiting metabolism) I would expect it would be simply additive.

 

[NeuroPsyence]

Thanks for the answers! This information was exactly what I was looking for.