Re: Correcting for salt vs. base

Hi Dennis, Your main question is a straightforward one -- both the dose and concentration should be expressed w/respect to the same entity. When the concentration is expressed in terms of base (the norm), it makes sense to express the dose in terms of base for PK analysis. What is in the label is another issue. There is a guidance (web site given below) from the FDA that says they will follow the USP Salt Policy which became effective in May 1, 2013. That policy states that, for newly approved drugs, "The strength also will be expressed in terms of the active moiety (e.g., "100 mg newdrug") rather than the salt strength equivalent (e.g., "123.7 mg newdrug hydrochloride")." www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM379753.pdf So, for paroxetine mesylate, which was approved July 2013, the package insert says, 'BRISDELLE is available as 7.5 mg pink capsules printed with black edible ink with “NOVEN” and “7.5 mg” on the capsule. Each capsule contains 9.69 mg paroxetine mesylate equivalent to 7.5 mg paroxetine base.' For mipomersen sodium, which was approved Jan 2013, the package insert says, 'Each vial or pre-filled string of KYNAMRO provides 200 mg of mipomersen sodium…' With this policy, it seems prudent to look at the package insert and check what the dose amount refers to, salt or base, because there are exceptions (see guidance) and you would have to know with certainty when the drug was approved to make a determination. Best regards, Nancy Nancy C Sambol, PharmD Associate Clinical Professor Dept of Bioengineering & Therapeutic Sciences Schools of Pharmacy & Medicine University of California San Francisco San Francisco CA 94143-0912 415-476-8884 [email protected]