2000 - Salamanca - Spain

PAGE 2000: poster
 

Kinetic behaviour of digoxin in a paediatric population

Martín-Suárez A1, Falcao AC2, Outeda M 3, Mora F4, González MC5, Quero M5, Arranz I4, Lanao JM1

1) Department of Pharmacy and Pharmaceutical Technology. University of Salamanca. 2) Laboratory of Pharmacology. Faculty of Pharmacy. University of Coimbra. 3) Pharmacy Service. Juan Canalejo Hospital. La Coruña. 4) Biochemical and 5)Cardiopaediatric Services. Ramón y Cajal Hospital. Madrid.

Some changes on digoxin disposition appear to be strongly correlated with normal physiological development during the first year of life. For this reason the relationship between digoxin pharmacokinetic parameters and age should be known in order to obtain appropriated serum drug concentrations in clinical practice. So, the aim of the present work is to study the evolution of the clearance of digoxin in paediatric patients.

A completely retrospective study was carried out using routine clinical care information obtained from patients taking digoxin and for whom the age range from 6 days to 1 year of life. All of them presented stable digoxin measurements (steady-sate condition) and blood samples were drawn during the second half of the dosing interval. The population analysis was performed using the NONMEM program. The data were fitted to the following one-compartment steady-state deterministic model:

Cmss = D . F/CL . II

where Cmss is the steady-state serum concentration (mcg/L), D is the maintenance dose of digoxin (mcg/kg), F is the bioavailability of digoxin (0.8 for elixir and 1 for IV doses), CL is the total body clearance (L/h kg), and II is the dosing interval (hours). The selected error models were proportional for the interindividual variability and additive for the residual variability.

The model-building process was carried out using the commonly adopted criteria for this kind of data analysis: behaviour of objective function, AIC criteria, graphical analysis, and predicted-observed correlation. The final selected model is the following one: CL (L/h/kg) = 0.232 (1 + 0.117*AGE (months))

Interindividual variability (CV) = 13% Residual variability (CV) = 0.32

As we can see, the final model denounce an increased digoxin clearance with age which means that doses (dose/kg) should be adapted progresively with age during the first year of life.




Reference: PAGE 9 (2000) Abstr 127 [www.page-meeting.org/?abstract=127]
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