Drug Groups

approved; investigational

Description

Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the FDA in late May 2007, and was also approved by the European Medicines Agency (EMEA) on November 2007. It is a derivative of sirolimus and is sold as Torisel.

Indication

For the treatment of renal cell carcinoma (RCC). Also investigated for use/treatment in breast cancer, lymphoma (unspecified), rheumatoid arthritis, and multiple myeloma.

Toxicity

Temsirolimus has been administered to patients with cancer in phase 1 and 2 trials with repeated intravenous doses as high as 220 mg/m2. The risk of several serious adverse events, including thrombosis, bowel perforation, interstitial lung disease (ILD), seizure, and psychosis, is increased with doses of temsirolimus greater than 25 mg.

Affected Organisms

Biotransformation

Primarily metabolized by cytochrome P450 3A4 in the human liver. Sirolimus, an equally potent metabolite, is the primary metabolite in humans following IV infusion. Other metabolic pathways observed in in vitro temsirolimus metabolism studies include hydroxylation, reduction and demethylation.

Absorption

Infused intravenous over 30 - 60 minutes. C_max is typically observed at the end of infusion

Half Life

Temsirolimus exhibits a bi-exponential decline in whole blood concentrations and the mean half-lives of temsirolimus and sirolimus were 17.3 hr and 54.6 hr, respectively.

Protein Binding

87% bound to plasma proteins in vitro at a concentration of 100 ng/ml

Elimination

Excreted predominantly in feces (76%), 4.6% of drug and metabolites recovered in urine. 17% of drug was not recovered by either route following a 14-day sample collection.

Distribution

172 L in whole blood of cancer patients; both temsirolimus and sirolimus are extensive distributed partitioned into formed blood elements

Clearance

16.2 L/h (22%)

References

External Links