Abstract:
INTRODUCTION : Clinicians’ skepticism, fueled by evidence of inferiority of some multisource
generic antimicrobial products, results in the underutilization of more cost-effective generics,
especially in critically ill patients. The aim of this observational study was to demonstrate
equivalence between the generic or comparator brand of meropenem (Mercide®) and the leading
innovator brand (Meronem®) by means of an ex vivo technique whereby antimicrobial activity
is used to estimate plasma concentration of the active moiety.
METHODS : Patients from different high care and intensive care units were recruited for observation
when prescribed either of the meropenem brands under investigation. Blood samples
were collected over 6 hours after a 30 minute infusion of the different brands. Meropenem
concentration curves were established against United States Pharmacopeia standard meropenem
(Sigma-Aldrich) by using standard laboratory techniques for culture of Klebsiella pneumoniae.
Patients’ plasma samples were tested ex vivo, using a disc diffusion assay, to confirm antimicrobial
activity and estimate plasma concentrations of the two brands.
RESULTS : Both brands of meropenem demonstrated similar curves in donor plasma when concentrations
in vials were confirmed. Patient-specific serum concentrations were determined from
zones of inhibition against a standard laboratory Klebsiella strain ex vivo, confirming at least
similar in vivo concentrations as the concentration curves (90% confidence interval) overlapped;
however, the upper limit of the area under the curve for the ratio comparator/innovator exceeded
the 1.25-point estimate, i.e., 4% higher for comparator meropenem.
CONCLUSION : This observational, in-practice study demonstrates similar ex vivo activity and in
vivo plasma concentration time curves for the products under observation. Assay sensitivity is
also confirmed. Current registration status of generic small molecules is in place. The products
are therefore clinically interchangeable based on registration status as well as bioassay results, demonstrating sufficient overlap for clinical comfort. The slightly higher observed comparator
meropenem concentration (4%) is still clinically acceptable due to the large therapeutic index
and should ally fears of inferiority.
