CASE STUDY: IMPROVING THE BIOAVAILABILITY OF A COMPOUND BY 10-FOLD.

CanAm Bioresearch was approached by a client who had a compound with bioavailability less than 10%. The client's main goal was to enhance the compound's bioavailability.

Goal: To increase the bioavailability of the compound.

Services provided by CanAm: Project leadership, medicinal chemistry and analytical chemistry services.

As per Chapter 21 CFR (Codes of Federal Regulations) Part 320.1, bioavailability of a drug is defined as the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action.

The compound provided by the client contained a phosphate functional group in its chemical structure. At physiological pH, the phosphate functional group is charged which hinders the compound’s membrane permeability, resulting in diminished absorption and bioavailability. Our team decided to design phosphate prodrugs after examining the compound’s structure. They modified the acidic oxygen by adding labile protecting groups to produce a charge-neutral compound. This strategic approach led to improved absorption and enhanced bioavailability, propelling the modified compound to become a drug candidate for advanced clinical studies.

Over the course of the project, the CanAm team designed numerous compounds and conducted several scale-ups. The bioavailability studies of the compounds were also carried out at CanAm. Within six months, the CanAm team provided a new chemical entity to the client that was marked as a candidate for human clinical studies. At CanAm, we prioritize the swift protection of intellectual property and utilize a flexible resource approach. What began as a project involving 3 chemists, evolved quickly into an initiative that included 7 chemists.

Result: The new chemical entity has a bioavailability that is ten times that that of the initial compound, leading to the advancement of the drug compound for human clinical studies.