Podophyllotoxin Other names: Podofilox

Podophyllotoxin is a metaphase inhibitor in dividing cells binding to at least one binding site on tubulin. Binding prevents tubulin polymerisation required for microtubule assembly. At higher concentrations, podophyllotoxin also inhibits nucleoside transport through the cell membrane.

The chemotherapeutic action of podophyllotoxin is assumed to be due to inhibition of growth and the ability to invade the tissue of the viral infected cells.

Systemic absorption of podophyllotoxin after topical application of 100 mg of 0.3% cream or 100 μL of 0.5% solution has been studied (extravaginally in 10 females, and within the preputial cavity in 10 males, each on 2 occasions separated by 8 hours). C_max was at or below 4.7 ng/mL following all doses and T_max ranged from 0.5 to 36 hrs; in some subjects concentrations were below the limit of detection. The C_max and T_max were comparable for the 0.3% cream and 0.5% solution in both males and females. It can be concluded that systemic absorption of recommended doses of podophyllotoxin cream or solution is expected to be low.

Carcinogenesis/Mutagenesis

Podophyllotoxin was not carcinogenic following dietary administration up to 0.3 mg/kg/day for 104 weeks in rats and 80 weeks in mice.

Podophyllotoxin was not mutagenic in in vitro Ames Assays, mouse lymphoma assay, and human lymphocyte metaphase assay. Podophyllotoxin showed evidence of mutagenicity in in vitro HPRT mutation assays, however results were inconsistent with regard to the dose response observed across replicate cultures. In mouse micronucleus studies, results were also inconsistent as one study did not show evidence of mutagenicity and one study did show evidence of an aneugenic effect (increased incidence of micronucleated polychromatic erythrocytes, mitotic arrest). Podophyllotoxin did induce aneuploidy in hamster oocytes.

Reproductive Toxicology

Fertility

In a multi-generational rat fertility and general reproductive performance study, podophyllotoxin administered orally up to 2.5 mg/kg/day had no effect on fertility in female or male rats.

Pregnancy

Podophyllotoxin was not teratogenic in rabbits administered up to 0.5% podophyllotoxin topically or in rats administered up to 5 mg/kg/day intraperitoneally.