Estimating drug-free period using a graphical method: an alternative way to monitor extended-interval dosing of...

Published nomograms to monitor extended-interval dosing (EID) gentamicin therapy were based on a fixed dose of 5 or 7 mg/kg. However, the average dose used for EID gentamicin regimen in our setting was about 3 mg/kg per day. We developed a new method of monitoring based on the duration of drug-free period (DFP) in a 24-h dosing interval.

Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (K_e ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.

Correlation between K_e and age was favourable (r = -0.453; P = 0.001). K_e derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P < 0.001). On this basis, two curves representing minimum and maximum DFPs of 2 and 8 h, respectively, were constructed. The final coordinates, which were plotted from an empirically estimated K_e and a 6 h postdose concentration, were used to determine whether the DFP was within the targeted range.

We have proposed using DFP to monitor EID of gentamicin therapy. A graphical method offers a convenient way to estimate this parameter.