Synthesis and pharmacokinetic and pharmacodynamic evaluation of the forodesine HCl analog BCX-3040
Hollis S Kezar1, J Michael Kilpatrick, Deborah Phillips
1BioCryst Pharmaceuticals Inc., Birmingham, Alabama 35244, USA.
Abstract:
Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP) and is currently in clinical trials for the treatment of leukemia and lymphoma. Animal models indicated that forodesine HCl would have low oral bioavailability in humans and it was initially developed as an intravenous formulation. We were interested in identifying analogs of forodesine HCl with improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl.
Related Concept Videos
Pharmacodynamics: Overview and Principles
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or within...
Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Drug Discovery: Overview
Drug Administration and Therapy Phases: Overview
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
Preclinical Development: Overview
Measurement of Bioavailability: Pharmacodynamic Methods

