Fig. 7.

Correlation of in vitro drug release and in vivo pharmacodynamics. a The dose amounts released in peritoneal cavity for the nine drug treatment groups were simulated based on the in vitro drug release profiles. Pac/Crem 40 × 1 refers to a single treatment of paclitaxel/Cremophor micellar solution at 40 mg/kg. Abbreviations for single type microparticles are as follows: MP (dose) (type of microparticles). Abbreviations for combination microparticles are as follows: MP (dose of first microparticles) (type of first microparticles) (dose of second microparticles) (type of second microparticles). Abbreviations for repeated treatments are as follows: Pac/Crem 40 × 3 is 3 weekly treatments of 40 mg/kg on days 0, 7, and 14 post-treatment (equivalent to 10, 17, and 24 days post tumor-implantation). MP40SF80SSx2 is two treatments of MP40SF plus MP80SS given on days 0 and 21 post-treatment (equivalent to 10 and 31 days post tumor-implantation). b In vivo biological activity. Day 0 represents the day of treatment initiation, which corresponded to 10 days post-tumor implantation (about 40% of the MST of controls). Survival over time is shown in Kaplan Meier curves. c Correlation of simulated drug release in peritoneal cavity and in vivo pharmacodynamics. Open circle paclitaxel/Cremophor; solid circle TPM. Treatment efficacy was expressed in median survival time (MST). The drug amount released in peritoneal cavity at MST for individual treatments were obtained from the data in panel b. The best-fit linearly regressed lines were MST = 0.39 × (released dose) + 19 for microparticles (r ² = 0.86, p = 0.0003) and MST = 0.15 × (released dose) + 17 for paclitaxel/Cremophor (r ² = 0.85, p = 0.1). The data points at 0 mg/kg correspond to the respective vehicle control for each group (saline and blank microspheres). Reprinted with permission (8)