BACKGROUND: There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area. PROCEDURE: Leukemia patients treated according to the Interfant 99 protocol received 30 mg/m(2) daunorubicin, with dose reduction to 3/4 for patients 6-12 months old and 2/3 for patients <6 months, respectively. Plasma samples from 21 patients (aged 0.05-1.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6-18.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM. RESULTS: Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9 L hr(-1) m(-2) +/- 65% and central volume of distribution 16.4 L m(-2) +/- 46%, whereas apparent clearance of daunorubicinol was 19.1 L hr(-1) m(-2) +/- 32% and apparent volume of distribution 228 L m(-2) +/- 80% (mean +/- interindividual variability). No age-dependency in any of the BSA-normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged <6 months experienced more infections in the induction phase than the group aged 6-12 months at diagnosis. Other toxicities were similar in both groups. CONCLUSION: We observed no indication of an age-dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355-360. Copyright 2009 Wiley-Liss, Inc.
BACKGROUND: There is an extreme paucity of pharmacokinetic data for anticancer agents in infants. Therefore, we aimed at characterizing the pharmacokinetics for daunorubicin in infants and examined their relationship to age, body weight, and body surface area. PROCEDURE: Leukemiapatients treated according to the Interfant 99 protocol received 30 mg/m(2) daunorubicin, with dose reduction to 3/4 for patients 6-12 months old and 2/3 for patients <6 months, respectively. Plasma samples from 21 patients (aged 0.05-1.88 years) were collected and analyzed for daunorubicin and daunorubicinol. Samples from 12 children (age 1.6-18.8 years), who received daunorubicin in an earlier investigation, were used for pharmacokinetic model building using the software NONMEM. RESULTS: Plasma concentration time profiles could be described using a two compartment model. Daunorubicin clearance was 43.9 L hr(-1) m(-2) +/- 65% and central volume of distribution 16.4 L m(-2) +/- 46%, whereas apparent clearance of daunorubicinol was 19.1 L hr(-1) m(-2) +/- 32% and apparent volume of distribution 228 L m(-2) +/- 80% (mean +/- interindividual variability). No age-dependency in any of the BSA-normalized pharmacokinetic parameters was observed. Consequently, due to the empirical dose reduction in infants the overall exposure to daunorubicinol in infants was smaller than would be expected from older children. Patients aged <6 months experienced more infections in the induction phase than the group aged 6-12 months at diagnosis. Other toxicities were similar in both groups. CONCLUSION: We observed no indication of an age-dependency in the pharmacokinetics of daunorubicin. Pediatr Blood Cancer 2010;54:355-360. Copyright 2009 Wiley-Liss, Inc.
Authors: Johan G C van Hasselt; Natasha K A van Eijkelenburg; Jos H Beijnen; Jan H M Schellens; Alwin D R Huitema Journal: Br J Clin Pharmacol Date: 2013-07 Impact factor: 4.335
Authors: Swantje Völler; Joachim Boos; Miriam Krischke; Gudrun Würthwein; Nina E Kontny; Alan V Boddy; Georg Hempel Journal: Clin Pharmacokinet Date: 2015-11 Impact factor: 6.447
Authors: Wanda L Salzer; Tamekia L Jones; Meenakshi Devidas; Joanne M Hilden; Naomi Winick; Stephen Hunger; William L Carroll; Bruce Camitta; ZoAnn E Dreyer Journal: Pediatr Blood Cancer Date: 2012-04-05 Impact factor: 3.167