A multi-centre, phase IV study to evaluate the steady-state plasma concentration and serum bactericidal activity of a generic teicoplanin preparation

Abstract

Introduction:Teicoplanin is an effective treatment option against methicillin-resistant, Gram-positive bacteria, like Staphylococcus aureus. It is a glycopeptide antibiotic, produced through microbial fermentation, a process resulting in variations in the N-acyl side chain. Concerns that these variations may affect the pharmacokinetic profile and the clinical efficacy of generic teicoplanin preparations have been raised. Method: To address this issue, a multi-centre observational study was conducted to evaluate steady-state peak and trough serum concentrations, and the serum bactericidal activity (SBA) and safety of a generic teicoplanin preparation in critically ill patients. Additionally, the composition of the generic teicoplanin was compared to that of the innovator drug to assess differences in the composition. Results: Following pre-determined loading and maintenance dose schedules, the mean peak and trough teicoplanin serum concentrations were 20.98 mg/l and 10.38 mg/l, respectively. A statistically significant association was observed between teicoplanin pharmacotherapy and increased ex vivo SBA. It was found using independent analysis that the composition of the generic teicoplanin preparation was similar to that of the innovator drug, and that both formulations met the European Pharmacopoeia specifications. Conclusion:The loading and maintenance schedules employed in this study were effective in establishing therapeutic serum teicoplanin concentrations in critically ill patients. Evidence of bactericidal activity measured in patients' ex vivo serum samples, following treatment with the generic preparation, supports this finding.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice

“…Such studies have been conducted to examine serum concentrations of lithium in adults with bipolar disorder for prophylaxis of mania [31] and serum concentrations of teicoplanin in adults who are critically ill with gram negative infections [32]. …”

“…The most useful studies are well designed randomised controlled trials (RCTs) comparing two or more therapeutic ranges for the same drug, and reporting clinically relevant outcomes. Such studies have been conducted to examine serum concentrations of lithium in adults with bipolar disorder for prophylaxis of mania [ 31 ] and serum concentrations of teicoplanin in adults who are critically ill with gram negative infections [ 32 ].…”