1 / 9

Tazarotene Toxicity Studies

Toxicology Studies of Tazarotene Jiaqin Yao, Ph.D., Toxicologist Division of Dermatologic and Dental Drug Products FDA/CDER/OND/ODE V. Tazarotene Toxicity Studies.

riva
Download Presentation

Tazarotene Toxicity Studies

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Toxicology Studies of TazaroteneJiaqin Yao, Ph.D., ToxicologistDivision of Dermatologic and Dental Drug ProductsFDA/CDER/OND/ODE V

  2. Tazarotene Toxicity Studies • Oral administration of tazarotene in rats (3 to 6 months), dogs (4 to 9 months), and monkeys (1month to 1 year) produced effects that were characteristic of retinoid toxicity • Maximum systemic exposure (AUC) to tazarotenic acid in these studies was generally similar or greater than (dogs), or less than (rats and monkeys) systemic exposure in humans at the recommended daily oral dose (4.5 mg). • Primary target organs/systems included bone, liver (including serum lipids), kidney, heart, thymus, testis, and skin. • Tazarotene was not a genotoxic substance, neither was it a carcinogen in rats and mice.

  3. Toxicity in Fertility and Early Embryonic Development

  4. Toxicity in Embryonic Development

  5. Toxicity in Prenatal and Postnatal Development

  6. Male Reproductive Toxicity

  7. Maximum Recommended Human Dose (mg/kg/day) * proposed

  8. Lowest Teratogenic Dose (mg/kg/day) a Pharmac. Ther. 40:29-43, 1989 b Toxicology 57:117-161, 1989 c J. Am. Acad. Dermatol. 6:652-659, 1982 d Not detectable

  9. Conclusions • Human may be the most sensitive species for teratogenicity of retinoids. • Tazarotene is a more potent teratogen than other retinoids in rats and rabbits on a mg/kg/day basis. • Tazarotene is a probable human teratogen.

More Related