Microbiological Equivalence of Bacteriostatic and Bactericidal Activities of the Sera from Healthy Volunteers Receiving Generic Piperacillin/Tazobactam (PipertazR) and Original Piperacillin/Tazobactam (TazocinR)
Visanu Thamlikitkul MD*, Surapee Tiengrim MSc*, Chalobol Chalermsri MD**, Ratikorn Sae-Jong MD**, Siriluk Suddhichupaiboon MSc***
Affiliation : * Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand ** Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand *** Siriraj Clinical Research Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Background : Several generic piperacillin/ tazobactam formulations have been approved by Thai Food and Drug Administration,
Ministry of Public Health. Piperacillin/ tazobactam is a parenteral drug. Therefore, a study demonstrating a biological
equivalence of generic piperacillin/ tazobactam is not required for drug registration in Thailand.
Objective : The study was to determine microbiological equivalence of serum bacteriostatic and bactericidal activities of the
sera from healthy volunteers receiving generic piperacillin/ tazobactam (PipertazR) and original piperacillin/tazobactam
(TazocinR).
Material and Method: This was a randomized crossover study in 16 adult healthy volunteers. Each subject received 4.5
grams of PipertazR and TazocinR in 50 ml of normal saline via intravenous infusion for 30 minutes. The blood samples were
drawn at baseline prior to receiving the study drug, at 30 minutes after initiating infusion, and at 8 hours after initiating
infusion. The serum bacteriostatic activity against E. coli ATCC 25922, K. pneumoniae, P. aeruginosa ATCC 27853 and A.
baumannii was performed by disk diffusion The serum bactericidal activity against E. coli ATCC 25922 was performed by
Serum Bactericidal Titre.
Results : The average inhibition zone diameter of the serum samples from the subjects while receiving PipertazR against each
tested organisms was < 1 mm smaller than that while receiving TazocinR and such difference was not significantly different.
All serum samples collected at 30 minutes after initiating TazocinR and Pipertaz R had bactericidal titres 1:64 to 1:256 against
E. coli ATCC 25922. All serum samples collected at 8 hours after initiating TazocinR and PipertazR had bactericidal titres <
1:2 against E. coli ATCC 25922. The differences of serum bactericidal titres of the serum samples collected at 30 minutes (p
= 0.7) and 8 hours (p = 1.0) after initiating TazocinR and PipertazR were not statistically significant.
Conclusion : The sera from healthy volunteers receiving PipertazR contain bacteriostatic and bactericidal activities not
significantly different from those receiving TazocinR.
Keywords : Microbiological equivalence, Generic drug, Piperacillin/ tazobactam
