Medical Pharmacology Chapter 33-34: Anticancer Drugs
Antifolate Analogues: Pralatrexate (Folotyn)
Pralatrexate (Folotyn) is another antifolate analog which inhibits DNA, RNA and protein synthesis by means of competitive inhibition for the dihydrofolate reductase:folate binding site.3
Pralatrexate is a 10-deaza-aminopterin antifolate analog.
This analog was intended to be a better substrates for the RFC-1 (reduce folate) carrier protein.
Pralatrexate not only inhibits dihydrofolate reductase but also inhibits enzymes associated with de novo purine nucleotide biosynthesis as well as inhibiting thymidylate synthase.3
Similar to methotrexate and pemetrexed, this agent is excreted in the urine and in the presence of renal disease may require dose adjustments.
Pralatrexate following cell entry is polyglutamylated by the enzyme folylpolyglutamate synthetase.
This drug is not significantly metabolized either by phase I metabolism (cytochrome P450 microsomal metabolizing system) or by phase II glucuronidases.7
The drug is primarily excreted unchanged (urine: about 34%-39%; feces about 34%; respiratory about 10%, exhaled).
The elimination half-life is about 12-18 hours.
The principal labeled indication is in the treatment of relapsed or refractory peripheral T-cell lymphoma. (Labeled Use)7
With respect off label use, pralatrexate may be helpful in treating relapsed or refractory cutaneous T-cell lymphomas (CTCL)8
Principal side effects: myelosupression, skin rash, diarrhea, mucositis, fatigue.
Toxicities related to pralatrexate administration may be diminished with folic acid and vitamin B12 vitamin supplementation.