STUDIES ON DRUG-MONITORING IN THRICE AND ONCE-DAILY TREATMENT WITH AMINOGLYCOSIDES

Objectives: To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring. Design: The design of the study was a consecutive sample trial. Setting: The study took place in a university hospital. Patients: 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study. Interventions: In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed. Measurements and results: In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value. Conclusions: The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important.