Limited sampling strategies for determining the area under the plasma concentration-time curve for isoniazid might be a valuable approach for optimizing treatment in adult patients with tuberculosis

International Journal of Antimicrobial Agents
Piergiorgio CojuttiFederico Pea

Abstract

This study aimed to develop clinically feasible models of limited sampling strategy (LSS) for estimation of the area under the concentration-time curve (AUC24h) for isoniazid, that could be applied easily in daily clinical practice for dosage adjustment in adult patients with tuberculosis. Isoniazid plasma concentrations (n = 1665) from 185 adult tuberculous patients were used for the development and validation of LSS models to estimate AUC24h following administration of the standard 5 mg/kg dose of isoniazid. Population pharmacokinetic analysis for appropriate estimation of isoniazid pharmacokinetic parameters was performed in a modelling group (n = 100). The Bayesian estimates of AUC24h (AUCref) obtained for each individual were used as the dependent variable in the regression analysis for the development of various LSS models. The LSS models were validated in a separate cohort (n = 85). Several three and four time point LSS models were built and tested. Model H (AUC24h = -1.88 + 1.05 × C1 + 0.78 × C2 + 9.44 × C5) and Model I (AUC24h = -0.65 + 1.00 × C1 + 1.94 × C2 + 15.45 × C9) had the best performances [adj-R2 = 0.93, median prediction error (MPE) = -0.20, root median squared prediction error (RMSE) = 4.65 for Model H; adj-...Continue Reading

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