Farmacocinética poblacional de cisplatino aplicada a la personalización de su dosificación en pacientes oncológicos
2012
Objective: To develop and internally validate a population pharmacokinetics model for cisplatin
and assess its prediction capacity for personalising doses in cancer patients.
Method: Cisplatin plasma concentrations in forty-six cancer patients were used to determine
the pharmacokinetic parameters of a two-compartment pharmacokinetic model implemented in
NONMEN VI software. Pharmacokinetic parameter identification capacity was assessed using the
parametric bootstrap method and the model was validated using the nonparametric bootstrap
method and standardised visual and numerical predictive checks. The final model’s prediction
capacity was evaluated in terms of accuracy and precision during the first (a priori) and second
(a posteriori) chemotherapy cycles.
Results: Mean population cisplatin clearance is 1.03 L/h with an interpatient variability of
78.0%. Estimated distribution volume at steady state was 48.3 L, with inter- and intrapatient
variabilities of 31,3% and 11,7%, respectively. Internal validation confirmed that the population
pharmacokinetics model is appropriate to describe changes over time in cisplatin plasma concentrations,
as well as its variability in the study population. The accuracy and precision of a
posteriori prediction of cisplatin concentrations improved by 21% and 54% compared to a priori
prediction.
Conclusion: The population pharmacokinetic model developed adequately described the changes
in cisplatin plasma concentrations in cancer patients and can be used to optimise cisplatin
dosing regimes accurately and precisely.
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