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

Objective: To evaluate the pharmacokinetic appropriateness of a possible sw itch in dosing schedule for outpatients after hospital discharge, i.e. the bioequivalence of a single 400mg intravenous daily dose versus double-refra cted 200mg intramuscular doses. Subjects and Methods: This study was conducted in 10 normal healthy volunte ers using a two-way randomised, open-label, two-period crossover design. Ea ch subject received two different drug regimens of teicoplanin: a single 40 0mg intravenous daily dose versus double daily refracted 200mg intramuscula r doses. Teicoplanin serum concentrations were analysed by means of a fluor escence polarisation immunoassay system in samples collected for up to 72 h ours after each regimen. Pharmacokinetic evaluations were performed by mean s of a 3-compartment open model with first-order elimination using the WinN onlin 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 400mg intravenous d ose, and after the first and second intramuscular administrations, respecti vely. The trough level at 24 hours (C-24)was 4.55 +/- 1.04 mg/L after the 4 00mg intravenous dose, and 6.67 +/- 1.75 mg/L after double 200mg intramuscu lar doses. The ratio between C-24 intramuscular and intravenous treatment w as 1.46 +/- 0.17. Total body exposure (AUC(0-infinity)) was 474.22 +/- 111. 77 mg/L.h post-intravenous dose, and 424.84 +/- 113.53 mg/L.h post-intramus cular doses. Intramuscular bioavailability suggested substantial bioequival ence with intravenous administration (89.58 +/- 14.35%). Dose-normalised da ta indicated that the intersubject variability was mainly related to interi ndividual differences in bodyweight. Conclusion: These findings indicated that a total daily dosage of teicoplan in 400mg administered in two refracted doses by the intramuscular route cou ld produce steady-state trough levels that are even higher than those achie vable after once-daily intravenous administration during maintenance treatm ent. 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 fr om intravenous to intramuscular therapy in outpatients at the moment of hos pital discharge (changing therapy from 400mg intravenously once daily to 20 0mg intramuscularly twice daily) may be reliably proposed, allowing better compliance without reducing efficacy.