Bioequivalence and Bioavailability Forum

Hi Mustafa,

what is the rationale behind your question - because you have posted in the 'Bioanalytics'-category? Are you concerned about getting the calibration range range right?

❝ [...] CV values of drugs that are considered as highly variable drugs, e.g simvastatin, itraconazole, lamivudine, etc.

I'm afraid that any literature search for HVDs will give you quite incomplete results. You only can search for a particular drug and then try to get the CV (HVD >30%) from the studies' results. If the CV is not given, calculate it from the confidence interval & sample size - see one of Helmut's lectures (slides 10-16).

❝ [...] i need to confirm whether certain active ingredients are highly variable or not.

Don't mix up HVDs (Highly Variable Drugs) and HVDPs (Highly Variable Drug Products). HVDs show CV >30% if administered as a solution, i.e. the variability is caused by highly variable clearance. HVDPs are not necessarily HVDs also. See the results for diclofenac in one of Helmut's presentations: A solution shows a CV of only ~7%, effervescent tablets and IR ~12%, delayed release after a single dose ~22%, and dermal ~33%.

Dear Mr.Mustafa,

Check out the CHMP assessment report on Lamivudine which discuss about the intrasubject CV% in a bioequivalence study in the following link
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001111/WC500044180.pdf

Find the intrasubject CV% of Simvastatin and Itraconazole in the Public assessment report of Itraconazole and Simvastatin in the following links
http://www.lakemedelsverket.se/SPC_PIL/Pdf/par/Simvastatin%20Morningside,%20film-coated%20tablets.pdf
http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con046562.pdf

Regards,

Dr.S.Gunasakaran, MD