[Pharmacokinetics of SK & F 104864 in experimental animals. I. Plasma level]

A camptothecin derivative, SK & F 104864 (topotecan), was injected for 30 minutes into the rabbit ear vein at a dose of 2 mg/kg or 5 mg/kg, and the plasma concentration was assayed by a HPLC method. The plasma level of SK & F 104864 (lactone form) decreased bi-exponentially with mean alpha and beta half-lives of 0.101 h and 0.849 h at 2 mg/kg, respectively, and 0.518 h and 7.57 h at 5 mg/kg, respectively. The AUCs were 0.846 micrograms.h/ml at 2 mg/kg and 2.14 micrograms.h/ml at 5 mg/kg. The plasma level of total topotecan (SK & F 104864 plus SK & F 105992) decreased bi-exponentially with mean alpha and beta half-lives of 0.696 h and 9.07 h at 2 mg/kg, respectively, and 0.795 h and 8.97 h at 5 mg/kg, respectively. The AUCs were 2.15 micrograms.h/ml at 2 mg/kg and 5.73 micrograms.h/ml at 5 mg/kg. The AUCs of lactone form were 39.3% of total topotecan at the 2 mg/kg dose and 37.3% at the 5 mg/kg dose, respectively. After intravenous bolus injection of SK & F 104864 at 20 mg/kg into Sarcoma 180 bearing mice, the alpha and beta half-lives of SK & F 104864 were 0.401 h and 3.99 h, respectively, and the AUC was 5.49 micrograms.hr/ml. The alpha and beta half-lives of total topotecan were 0.517 h and 4.27 h, respectively, and the AUC was 9.88 micrograms.hr/ml. The ratio of lactone form to total topotecan was 55.6%.