Abstract
Pharmacokinetically guided dosing was performed in nine paediatric patients receiving etoposide. Doses on day 2 of a 2- or 3-day schedule were adapted on the basis of the day-1 area under the plasma etoposide concentration vs time curve (AUC). The day-1 AUC was estimated using a limited sampling model and the day-2 target AUC defined by the etoposide dose-AUC 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 and with little bias (mean error 11% and root mean squared error 15% respectively). Pharmacokinetic parameters were similar to those reported previously in children, although interpatient pharmacokinetic variability was less than that observed previously: plasma clearance, 23 (18-26) ml 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). This study has demonstrated that pharmacokinetically guided dosing with etoposide is feasible. However, pharmacokinetically guided dosing is likely to be of most benefit in patients with abnormalities of renal or hepatic function, or in children with prior exposure to cisplatin.
Highlights
We have previously reported a limited sampling model for the estimation of etoposide area under the plasma concentration-time curve (AUC) in children after an intravenous dose, which is based upon a single etoposide sample taken at the end of a 1- to 4-h infusion (Lowis et al, 1993)
For day 2, the dose was calculated by multiplying the day-i dose by the ratio of the AUC observed on day 1, as measured by the limited sampling strategy, to the target AUC for that patient
To maintain the same overall dose in a given cycle, i.e. that which would have been given in the absence of adaptive dosing, a compensatory dose was given on day 3
Summary
The aim of the study was to examine the feasibility and accuracy of adaptively controlling etoposide dosing in children. The aims of this study were to document the feasibility and accuracy of adaptive control of etoposide therapy in children
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