PMID- 31140620
OWN - NLM
STAT- MEDLINE
DCOM- 20200921
LR  - 20210109
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 85
IP  - 9
DP  - 2019 Sep
TI  - Adjusted indirect comparisons to assess bioequivalence between generic 
      clopidogrel products in Serbia.
PG  - 2059-2065
LID - 10.1111/bcp.13997 [doi]
AB  - AIMS: Generic products can be regarded as therapeutically equivalent and 
      switchable with the reference product. However, switchability between generics is 
      unknown, as direct comparisons between generics are not performed. The aim of 
      this study was to investigate the bioequivalence between generic clopidogrel 
      products by means of adjusted indirect comparisons (AICs). METHODS: AICs were 
      conducted to assess bioequivalence between 4 generic clopidogrel products that 
      are authorised in Serbia. Generics are considered equivalent to the reference if 
      the 90% confidence intervals (CIs) for the ratios test/reference of the maximum 
      concentration (C(max) ) and area under the curve up to the last measurable 
      concentration (AUC(0-t) ) fall within the acceptance range 80.00-125.00%. 
      However, for AICs between generics, the Canadian acceptance criterion for C(max) 
      was employed, where only the point estimate of C(max) needs to be within 
      80.00-125.00%. RESULTS: The 90% CIs of the AICs demonstrated bioequivalence 
      within 80.00-125.00% for all AUC(0-t) comparisons. The point estimates of C(max) 
      in all AICs were also within this range. CONCLUSION: This study demonstrates that 
      the bioavailability of these 4 generic clopidogrel products authorised in Serbia 
      is very similar. Despite the limited power of AICs, bioequivalence was 
      demonstrated for all 90% CIs of AUC(0-t) and all 90% CIs of C(max) comparisons 
      were within or very close to the acceptance range, being able to comply with the 
      acceptance criterion employed in Canada for C(max) . Therefore, these 4 generic 
      clopidogrel products authorised in Serbia can be considered switchable with each 
      other in clinical practice based on the adjusted indirect comparisons.
CI  - (c) 2019 The British Pharmacological Society.
FAU - Pejcic, Zorica
AU  - Pejcic Z
AD  - Medicines and Medical Devices Agency of Serbia, Belgrade, Republic of Serbia.
AD  - Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - 
      Faculty of Pharmacy, Belgrade, Republic of Serbia.
FAU - Vucicevic, Katarina
AU  - Vucicevic K
AUID- ORCID: 0000-0001-9676-5785
AD  - Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - 
      Faculty of Pharmacy, Belgrade, Republic of Serbia.
FAU - Garcia-Arieta, Alfredo
AU  - Garcia-Arieta A
AUID- ORCID: 0000-0002-9702-6973
AD  - Division of Pharmacology and Clinical Evaluation Department of Human Use 
      Medicines, Spanish Agency for Medicines and Health Care Products, Madrid, Spain.
FAU - Miljkovic, Branislava
AU  - Miljkovic B
AD  - Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - 
      Faculty of Pharmacy, Belgrade, Republic of Serbia.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190707
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Drugs, Generic)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - A74586SNO7 (Clopidogrel)
SB  - IM
MH  - Area Under Curve
MH  - Biological Availability
MH  - Clopidogrel/*pharmacokinetics
MH  - Drugs, Generic/*pharmacokinetics
MH  - Humans
MH  - Platelet Aggregation Inhibitors/*pharmacokinetics
MH  - Serbia
MH  - Therapeutic Equivalency
PMC - PMC6710521
OTO - NOTNLM
OT  - bioequivalence
OT  - generic-generic substitution
OT  - interchangeability
OT  - switchability
OT  - therapeutic equivalence
COIS- There are no competing interests to declare.
EDAT- 2019/05/30 06:00
MHDA- 2020/09/22 06:00
PMCR- 2020/09/01
CRDT- 2019/05/30 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/04/11 00:00 [revised]
PHST- 2019/05/15 00:00 [accepted]
PHST- 2019/05/30 06:00 [pubmed]
PHST- 2020/09/22 06:00 [medline]
PHST- 2019/05/30 06:00 [entrez]
PHST- 2020/09/01 00:00 [pmc-release]
AID - BCP13997 [pii]
AID - 10.1111/bcp.13997 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2019 Sep;85(9):2059-2065. doi: 10.1111/bcp.13997. Epub 2019 
      Jul 7.