In the process of new drug (including herb-drug) development, some studies as followed you should be conducted.
1. In vitro metabolic stability study.
It will be conducted to understand wheather the parent of the new drug could be motabolised by CYP450 or UGT enzymes in liver for high rates of drug metabolism might result in low oral-bioaviability.
2. In vitro study on metabolism pathway identification
If the parent drug was metabolized by liver enzymes significantly, we need to know which isoforms of CYP450 participate in the process, which can be used to judge if co-administeration will effect the new drug’s effecacy and safety through inhibiting or inducing activities of these enzymes.
3. In vitro metabolite identification
And also we need to know what’s metabolites will be producted if the parent drug was metabolized by liver enzymes significantly, and the metabolites’ toxcity and efficacy if the metabolites is bioactive.
4. In vitro inhibition or induction study on CYP450 enzymes
We also need to know if the new drug inhibit or induce the activity of CYP450 enzymes, which might effect the efficacy and safety of other co-administration drugs.
5. Substrate Assay for Transporters
The studies should be conduct to understand if the drug was substrater or inhibitor of drug transporter, which will used to evaluate absorption, distribution and excretion of the drug.
6. In vitro metabolism profiling in animals and humans
The metabolism profiling should be conducted to understand which animal’s metabolism feature are similar with human, the results can provide evidences to animal selection of pre-clinical reseach.
7. Ex vivo liver cytochrome P450 isozyme profiling
After dosing the new drug to animals in pre-clinical experiment, the activities of metabolism enzyme should be evaluated by ex-vivo isozyme profiling.