Table 4

Delivery of desacetyl-vinblastine to tissues after multiple dose i.p. administration of vinblastine-conjugate and desacetyl-vinblastine at their respective MTDs

Tissues were obtained at various time points over a 24-h period after the last of five daily doses. AUC0–24 h values were calculated using mean concentrations (n = 2 to 3/time point).

Exposure ratio = [Desacetyl-vinblastine from vinblastine-conjugate (21.4 μmol/kg/day)]/[Desacetyl-vinblastine from desacetyl-vinblastine (0.26 μmol/kg/day)]
TissuedAc-vin from vin-conjugate AUC0–24 h (nm/h)dAc-vin from dAc-vin AUC0–24 h (nm/h)AUC ratio
Tumor878155316
Liver63459486.7
Kidney29440142920.6a
Brain371*b∼2c
Muscle912*∼5c
Plasma1212*∼6c
  • a May include contamination from residual urine.

  • b Insufficient concentration to calculate.

  • c Estimated using the assay quantification limit to calculate AUC in brain and muscle.