Yonsei Med J.  2020 Apr;61(4):301-309. 10.3349/ymj.2020.61.4.301.

Comparison of In Vivo Pharmacokinetics and Pharmacodynamics of Vancomycin Products Available in Korea

Affiliations
  • 1Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Korea. haroc153@naver.com, sijung@chonnam.ac.kr
  • 2Division of Clinical Pharmacology, Department of Pharmacology, Chonnam National University Medical School, Gwangju, Korea.
  • 3Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.

Abstract

PURPOSE
Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator.
MATERIALS AND METHODS
The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice.
RESULTS
Generic products had a lower proportion of vancomycin B (range: 90.3-93.8%) and a higher proportion of impurities (range: 6.2-9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (C(max)) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all p<0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (E(max)) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all p≤0.05).
CONCLUSION
Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in mice infected with hetero-vancomycin-resistant Staphylococcus aureus.

Keyword

efficacy; innovator; original; generic; Vancomycin

MeSH Terms

Animals
Chromatography, Liquid
In Vitro Techniques
Korea*
Mice
Pharmacokinetics*
Staphylococcus aureus
United States
Vancomycin*
Vancomycin
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