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

Yonsei Medical Journal 2020년 61권 4호 p.301 ~ 309
김희경 ( Kim Hee-Kyung ) - Chonnam National University Medical School Department of Infectious Diseases

최수미 ( Choi Su-Mi ) - Chonnam National University Medical School Department of Infectious Diseases
강가은 ( Kang Ga-Eun ) - Chonnam National University Medical School Department of Pharmacology
박경화 ( Park Kyung-Hwa ) - Chonnam National University Medical School Department of Infectious Diseases
이동건 ( Lee Dong-Gun ) - Catholic University College of Medicine Department of Internal Medicine
박완범 ( Park Wan-Beom ) - Seoul National University College of Medicine Department of Internal Medicine
 ( Rhee Su-Jin ) - Seoul National University College of Medicine Department of Clinical Pharmacology and Therapeutics
이승환 ( Lee Seung-Hwan ) - Seoul National University College of Medicine Department of Clinical Pharmacology and Therapeutics
정숙인 ( Jung Sook-In ) - Chonnam National University Medical School Department of Infectious Diseases
장희창 ( Jang Hee-Chang ) - Chonnam National University Medical School Department of Infectious Diseases

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 (Cmax) 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 (Emax) 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 hetero-vancomycin-resistant mice infected with Staphylococcus aureus.

키워드

Vancomycin; generic; original; innovator; efficacy
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