Pharmacokinetics and pharmacodynamics of sequential intravenous and subcutaneous teicoplanin in critically ill patients without vasopressors

Objective. To compare the pharmacokinetic parameters of sequential intravenous and subcutaneous teicoplanin in the plasma of surgical intensive care unit patients. Design and setting. Prospective, randomized, crossover study in the surgical ICU of a university hospital. Patients. Twelve patients with a suspected nosocomial infection, a serum albumin level higher than 10 g/l, body mass index less than 28 kg/m(2), and estimated creatinine clearance higher than 70 ml/min. Interventions. Teicoplanin was first administered intravenously as a loading dose of 6 mg/kg per 12 h for 48 h and then continued at a daily dose of 6 mg/kg. On the fourth day patients were randomized in two groups according to the order of the pharmacokinetic studies. Measurements and results. Serial plasma samples were obtained to measure teicoplanin levels. Compared with a 30-min intravenous infusion the peak concentration of teicoplanin after a 30-min subcutaneous administration occurred later (median 7 h, range 5-18) and was lower (16 mug/ml, 9-31; vs. 73, 53-106). Despite large and unpredictable interindividual differences no significant differences between subcutaneous and intravenous administration were observed in: trough antibiotic concentrations (10 mug/ml, 6-24; vs. 9, 5-30), the area under the teicoplanin plasma concentration vs. time curves from 0 to 24 h (AUC(0-24h); 309 mug/ml per minute, 180-640; vs. 369, 171-955), the proportion of the dosing interval during which the plasma teicoplanin concentration exceeded 10 mug/ml (96%, 0-100%; vs. 79%, 13-100%), and the ratio of AUC(0-24h) to 10 (77, 45-160; vs. 92, 43-239). Conclusions. In critically ill patients without vasopressors a switch to the subcutaneous teicoplanin after an initial intravenous therapy seems to give comparable pharmacodynamic indexes of therapeutic success.