A STUDY OF THE FEASIBILITY AND ACCURACY OF PHARMACOKINETICALLY GUIDEDETOPOSIDE DOSING IN CHILDREN

Pharmacokinetically guided dosing was performed in nine paediatric pat ients receiving etoposide, Doses on day 2 of a 2-or 3-day schedule wer e adapted on the basis of the day-1 area under the plasma etoposide co ncentration vs time curve (AUC). The day-1 AUC was estimated using a l imited sampling model and the day-2 target AUC defined by the etoposid e dose-AUG relationship observed in 33 children. Target AUC values (4. 6-8.2 mg ml(-1) x min) were achieved with a high degree of precision a nd with little bias (mean error 11% and root mean squared error 15% re spectively). Pharmacokinetic parameters were similar to those reported previously in children, although interpatient pharmacokinetic variabi lity was less than that observed previously: plasma clearance, 23 (18- 26) mi min(-1) m(-2); volume of distribution at steady state (Vdss), 6 .0 (3.9-8.9) l m(-2); t(1/2) 254 (127-550) min (median and range). Thi s study has demonstrated that pharmacokinetically guided dosing with e toposide is feasible. However, pharmacokinetically guided dosing is li kely to be of most benefit in patients with abnormalities of renal or hepatic function, or in children with prior exposure to cisplatin.