The plasma pharmacokinetics of FK463 were determined in neutropenic pediatric (2-12 years) and adult (>18 years) patients that participated in maximum tolerated dose studies. FK463 was administered as a 1-hour infusion to adults at fixed doses of 12.5 to 200 mg/day and to children at doses of 0.5 to 4.0 mg/kg/day. FK463 was well tolerated at all doses and no safety concerns were identified in either group. Serial blood samples were collected for plasma on Day 1, and on Day 4 in children or Day 7 in adults and subsequently analyzed by HPLC (LOQ = 0.05mcg/mL). A noncompartmental analysis of the data revealed that the area under the plasma concentrationtime curves to infinity (AUC(subscript: inf)) were doseproportional in children and adults and approximately 25-30% higher at steady-state. Mean terminal elimination half-life (t %) values for FK463 were approximately 11 to 17 hours in children and 10 to 16 hours in adults and they did not vary with time. On Day 1, mean clearance (CI) ranged from 0.257 to 0.419 mL/minlkg in children and from 0.206 to 0.253 mUmin/kg in adults. The mean terminal phase volume of distribution (V) ranged from 0.266 to 0.466 Ukg in children and from 0.246 to 0.271 L/kg in adults. AUC(subscript: 24) values on Day 4 in pediatric patients and on Day 7 in adults were similar to Day 1 AUC(supscript: inf )values at all dose levels; as were the CI and V values. Taken collectively, the data indicate that FK463 pharmacokinetics do not change appreciably in pediatric or adult patients and do not change appreciably after repeated administration over a wide dose range.
Full conference title:
Focus on Fungal Infections 11, March 14-16 2001
- Focus on Fungal Infection 11 (2001)