TABLE 6.

Summary of mean plasma protein binding for midostaurin, CGP52421 and CGP62221 in rat, dog, and human

Concentration Rat, fraction unboundDog, fraction unboundHuman, fraction unbound
ng/ml%
Midostaurin100–20,000**0.1 ± 0.02*,**0.08 ± 0.01*,**
Midostaurin100–10,000**0.01–0.02**
midostaurin20,0000.07
CGP52421 (epimers 1 and 2)141–39,700**0.239 ± 0.0351*,**
CGP52421 (epimers 1 and 2)319–45,200**0.204 ± 0.0454*,**
CGP52421 (epimers 1 and 2)1970–7790**0.0214 ± 0.0140**
CGP52421 (epimers 1 and 2)13,700–17,0000.155 ± 0.0332
CGP52421 (epimers 1 and 2)29,000–34,6000.202 ± 0.0412
CGP52421 (epimers 1 and 2)overall: 1970–34,600range: 0.0214–0.202
CGP62221860–27,200**0.227 ± 0.0907*,**
CGP62221925–47,300**0.193 ± 0.0140*,**
CGP622215470–6110**0.0375 ± 0.00605**
CGP6222110,100–11,4000.0976 ± 0.00252
CGP6222139,400–43,5000.198 ± 0.0140

  • ↵* Protein binding species difference compared with human.

  • ↵** denotes values at clinically relevant concentration ranges.