Therapeutic drug monitoring of gentamicin: evaluation of five nomograms for initial dosing at Al-Amiri Hospital in Kuwait

ABSTRACT

To compare five published nomograms [Thomson guidelines, Mawer nomogram, rule of eights, Hull-Sarubbi table and Dettli method] for calculating the initial gentamicin dosage regimen in a Kuwaiti population. Based on measured peak and trough gentamicin concentrations, the elimination rate constant and volume of distribution of gentamicin were calculated for each patient [n = 56], using a modified two-point Sawchuk-Zaske method. The calculated individual set of pharmacokinetic parameters and the initial dose regimen recommended by each of the five methods were used to predict the steady-state peak and trough of gentamicin concentrations. The Thomson guidelines produced consistent results in predicting gentamicin concentrations within the target ranges of peak plus trough, peak only and trough only [63, 75 and 75%, respectively]. The Mawer nomogram, Hull-Sa-rubbi table and Dettli methods achieved similar percentages of patients [46-50%] within the target ranges [5-10 mg l[-1] for peak and 0.5-2 for trough], whereas empirical dosing and the rule of eights showed the lowest percentages of patients within the peak plus trough target range [25 and 37%, respectively]. However, with respect to the underdosing target range [predicted concentration <5 mg l[-1]], the Thomson guidelines showed that 21% of patients were underdosed. The results show that a large number of patients [37-63%] were outside the target ranges in all initial gentamicin dosing methods evaluated in this study. Therefore, serum concentration measurement can be advised to assist in the optimization of gentamicin dose selection