Bioequivalence, antibacterial activity and therapeutic outcome of a generic meropenem (Mapenem).
BACKGROUND
The authors aimed to compare the bioequivalence and antibacterial activity of a generic meropenem with the original meropenem and studied its preliminary therapeutic outcome.


METHODS
A randomized, open-label, crossover study was employed to assess the bioequivalence and antibacterial activity. Twenty-six healthy males were recruited at Siriraj Hospital, Thailand and randomized to firstly receive either a single intravenous 30-minute infusion of a generic (Mapenem) or original meropenem (Meronem) and vice versa for the second period. The washout period was one week. Ten milliliters of blood samples were collected before meropenem infusion and at 0, 10, 15, 30, 45, 60, 90, 120, 150, 180, 240, 360, 470 and 480 minutes after the beginning of the drug infusion. Blood samples were coded and separated into plasma and serum samples. Plasma samples were used to determine drug concentrations by HPLC-UV detector and the data were analyzed for Cmax, AUC0-t and AUC0-inf. Serum samples were assayed in triplicate for measuring generic and original meropenems' inhibitory activities of a meropenem-susceptible E. coli ATCC 25922 in the same agar plate. An open-label design was used to preliminarily study of the therapeutic outcome and adverse effects of the generic meropenem in 30 patients.


RESULTS
All enrolled twenty-six volunteers completed the whole study. The statistical analysis of 90% confidence interval of Cmax, A UC0-t, and AUC0-inf of the generic and original meropenems were 87.7 to 101.7%, 96.3 to 102.4% and 96.3 to 102.3%, respectively. The results were within the standard range of bioequivalence acceptance criteria (80-125%) and the powers of the test were greater than 80%. Using E. coli ATCC 25922 in the blind assay of serum inhibition activity, the inhibitory zone sizes (mm) of the generic compared to original meropenems were not statistically different with respect to every time points of blood collections (p < 0.05). Correlation of mean values of serum meropenem levels and the widths of inhibitory zone sizes of the same samples collected at the same intervals showed good linear relationship with r = 0.891; R2 = 0.794 (p < 0.01) for the generic meropenem and r = 0.885; R2 = 0.784 (p < 0.01) for the original meropenem. The therapeutic result with the generic meropenem for various indications was successful or improved in 24 cases from 30 cases (80%) and the bacterial cure rate was 23 in 30 clinical isolates (76.7%). Adverse reactions probably related to the study medication were rash and elevated liver enzymes in 1 and 3 patients, respectively, and all resolved spontaneously.


CONCLUSIONS
In the present study, the generic meropenem exhibited indifferent bioequivalence and antibacterial activity compared to the original meropenem. There was also a good correlation between serum levels and inhibitory zone sizes produced by the same serum samples in every periods of blood collection. Clinical efficacy of the generic meropenem was shown to be satisfactory without notable severe adverse reaction.
Leelarasamee
Amorn
A
Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Rongrungruang
Yong
Y
Trakulsomboon
Suwanna
S
Pongpech
Pintip
P
Thanawattanawanich
Peeracha
P
Jithavech
Ponsiree
P
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D000077731:Meropenem; D013810:Therapeutic Equivalency; D013845:Thienamycins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D013845:Thienamycins; D000077731:Meropenem