Pharmacokinetics of 9-nitro-camptothecin in Beagle dogs

AIM: To study the pharmacokinetics of 9-nitro-camptothecin (9-NC) in dogs. METHODS: Each Beagle dog was given a single dose of 9-NC by iv or ig administration. The concentrations of 9-NC in plasma were detected by HPLC and HPLC-MS. Pharmacokinetic parameters were determined from the plasma concentration-time data with the 3P97 software package. The relationships between AUC, C_ max or ke and dose were evaluated by linear regression. RESULTS: After iv administration of 9-NC at the dose of 0.5, 1, and 2 mg·kg -1, the t_ 1/2 values of 9-NC were 2.2± 2.2, 1.8± 1.7 and 0.8± 0.6 h, respectively, and AUC_ 0-t were 105±71, 272±81 and 396±93 ng·h·ml -1, respectively. After ig administration of 9-NC at the dose of 1, 2, and 4 mg·kg -1, 9-NC was rapidly absorbed, reaching C_ max of 9.3± 8.2, 42±36 and 64±6 ng·ml -1 at T_ max of 0.3± 0.1, 0.2± 0.1, 0.4± 0.1 h, respectively, the t_ 1/2 values of 9-NC were 1.9± 1.3, 1.0± 0.6 and 2.8± 1.5 h, respectively, and AUC_ 0-t were 8.9± 7.2, 16±12 and 60±26 ng·h·ml -1, respectively. The values of t_ 1/2 and ke of 9-NC were independent of dose ([WTBX]P 0.05). The absolute oral bioavailability of 9-NC was less than 6%. CONCLUSION: After iv or ig administration of 9-NC, the time course of plasma concentration in dogs complies with a two-compartment model. The kinetic process of 9-NC in dogs is linear in the range of the experimental dosage. 9-NC is absorbed rapidly after ig administration and the oral bioavailability is poor. [WTHZ]