Table 5

Delivery of desacetyl-vinblastine to tissues after i.v. administration of single equimolar doses of vinblastine-conjugate and desacetyl-vinblastine

Tissues were obtained at various time points over a 24-h period after the tail vein administration of the indicated drug dose. AUC0–24 h values were calculated using a mean concentration of n = 3/time point. In this experiment, vinblastine-conjugate was given at less than half of its MTD, whereas desacetyl-vinblastine-treated animals were given a lethal dose of 35 times the MTD.

Exposure ratio = [Desacetyl-vinblastine from vinblastine-conjugate (9.2 μmol/kg)]/[Desacetyl-vinblastine (9.2 μmol/kg)]
dAc-vin from dAc-vin AUC0–24 h (nm/h)AUC ratio
TissuedAc-vin from vin-conjugate AUC0–24 h (nm/h)
Tumor251087400.29
Liver3650387500.094
Kidney8090984500.082
Brain*a288
Muscle*2140
Plasma234026800.87
• a Insufficient concentration to calculate.