Pharmacokinetic profile of two different administration schemes of teicoplanin. Single 400 mg intravenous dose vs double-refracted 200 mg intramuscular doses in healthy volunteers

Objective: To evaluate the pharmacokinetic appropriateness of a possible switch in dosing schedule for outpatients after hospital discharge, i.e. the bioequivalence of a single 400 mg intravenous daily dose versus double-refracted 200 mg intramuscular doses. Subjects and Methods: This study was conducted in 10 normal healthy volunteers using a two-way randomised, open-label, two-period crossover design. Each subject received two different drug regimens of teicoplanin: a single 400 mg intravenous daily dose versus double daily refracted 200 mg intramuscular doses. Teicoplanin serum concentrations were analysed by means of a fluorescence polarisation immunoassay system in samples collected for up to 72 hours after each regimen. Pharmacokinetic evaluations were performed by means of a 3-compartment open model with first-order elimination using the WinNonlin pharmacokinetic software package. Results: Teicoplanin peak serum concentrations were 97.96 ± 23.49 mg/L, 3.47 ± 1.00 mg/L and 6.99 ± 1.52 mg/L after a single 400 mg intravenous dose, and after the first and second intramuscular administrations, respectively. The trough level at 24 hours (C 24 ) was 4.55 ± 1.04 mg/L after the 400 mg intravenous dose, and 6.67 ± 1.75 mg/L after double 200 mg intramuscular doses. The ratio between C 24 intramuscular and intravenous treatment was 1.46 ± 0.17. Total body exposure (AUC(O-∞)) was 474.22 ± 111.77 mg/L·h post-intravenous dose, and 424.84 ± 113.53 mg/L·h post-intramuscular doses. Intramuscular bioavailability suggested substantial bioequivalence with intravenous administration (89.58 ± 14.35%). Dose-normalised data indicated that the intersubject variability was mainly related to interindividual differences in bodyweight. Conclusion: These findings indicated that a total daily dosage of teicoplanin 400 mg administered in two refracted doses by the intramuscular route could produce steady-state trough levels that are even higher than those achievable after once-daily intravenous administration during maintenance treatment. Since the time during which the serum concentration persists above MIC is actually thought to be a possible major determinant for the outcome of treatment with glycopeptides, this intramuscular schedule could enhance the pharmacokinetic exposure to teicoplanin. Therefore, a timely conversion from intravenous to intramuscular therapy in outpatients at the moment of hospital discharge (changing therapy from 400 mg intravenously once daily to 200 mg intramuscularly twice daily) may be reliably proposed, allowing better compliance without reducing efficacy.