Proposed approach to measuring TDM for raltegravir

Clinical studies have shown that the virological response to raltegravir is not linked to trough concentrations, but relates to AUC or “GMall” (geometric mean of all concentrations over 48 weeks).  However, obtaining a full AUC over the dosing interval is not practicable in clinical practice and so the use of alternative measurements were investigated.

Plasma concentrations and full AUCs were obtained from 47 HIV-negative volunteers receiving raltegravir (400 mg).  Trough concentrations were not significantly related to AUC0-12h or GMall.  The best single time point correlation with AUC0-12h was found with C2h (R2=0.815), but a stronger correlation (R2= 0.929) was found with AUC0-3h.


Assuming AUC to be the important PK parameter for raltegravir, then TDM should preferably use C2h or an abbreviated AUC0-3h to estimate reliably AUC0-12h, but these observations should be tested prospectively in a patient data set.

Ref: Burger D et al. AUC0-3h of raltegravir is correlated to AUC0-12h: a novel approach for therapeutic drug monitoring of raltegravir. 11th PK Workshop, 2010. Abstract 41.

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