Xin Li, Chenjing Wang, Ping Shi, Yanping Liu, Ye Tao, Pingping Lin, Ting Li, Haixun Hu, Feifei Sun, Shuqin Liu, Yao Fu, Yu Cao
{"title":"两种伏立康唑制剂在中国健康受试者静脉滴注后的药代动力学和安全性。","authors":"Xin Li, Chenjing Wang, Ping Shi, Yanping Liu, Ye Tao, Pingping Lin, Ting Li, Haixun Hu, Feifei Sun, Shuqin Liu, Yao Fu, Yu Cao","doi":"10.1186/s40360-023-00652-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole.</p><p><strong>Materials and methods: </strong>This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated.</p><p><strong>Results: </strong>The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C<sub>max</sub> was (2.552 ± 0.448) μg/mL, AUC<sub>0-t</sub> was (11.875 ± 7.157) h*μg/mL and AUC<sub>0-∞</sub> was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean C<sub>max</sub> was (2.615 ± 0.464) μg/mL, AUC<sub>0-t</sub> was (12.500 ± 7.257) h*μg/mL and AUC<sub>0-∞</sub> was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C<sub>max</sub> was (3.538 ± 0.691) μg/mL, AUC<sub>0-t</sub> was (24.976 ± 12.364) h*μg/mL and AUC<sub>0-∞</sub> was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean C<sub>max</sub> was (3.504 ± 0.667) μg/mL AUC<sub>0-t</sub> was (24.990 ± 12.455) h*μg/mL and AUC<sub>0-∞</sub> was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed.</p><p><strong>Conclusion: </strong>In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole.</p><p><strong>Trial registration: </strong>NCT05330000 (15/04/2022).</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985189/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects.\",\"authors\":\"Xin Li, Chenjing Wang, Ping Shi, Yanping Liu, Ye Tao, Pingping Lin, Ting Li, Haixun Hu, Feifei Sun, Shuqin Liu, Yao Fu, Yu Cao\",\"doi\":\"10.1186/s40360-023-00652-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole.</p><p><strong>Materials and methods: </strong>This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated.</p><p><strong>Results: </strong>The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C<sub>max</sub> was (2.552 ± 0.448) μg/mL, AUC<sub>0-t</sub> was (11.875 ± 7.157) h*μg/mL and AUC<sub>0-∞</sub> was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean C<sub>max</sub> was (2.615 ± 0.464) μg/mL, AUC<sub>0-t</sub> was (12.500 ± 7.257) h*μg/mL and AUC<sub>0-∞</sub> was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean C<sub>max</sub> was (3.538 ± 0.691) μg/mL, AUC<sub>0-t</sub> was (24.976 ± 12.364) h*μg/mL and AUC<sub>0-∞</sub> was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean C<sub>max</sub> was (3.504 ± 0.667) μg/mL AUC<sub>0-t</sub> was (24.990 ± 12.455) h*μg/mL and AUC<sub>0-∞</sub> was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed.</p><p><strong>Conclusion: </strong>In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole.</p><p><strong>Trial registration: </strong>NCT05330000 (15/04/2022).</p>\",\"PeriodicalId\":9023,\"journal\":{\"name\":\"BMC Pharmacology & Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-03-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985189/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Pharmacology & Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40360-023-00652-3\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pharmacology & Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40360-023-00652-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pharmacokinetics and safety of two Voriconazole formulations after intravenous infusion in two doses in healthy Chinese subjects.
Background: Voriconazole is a second-generation triazole that is used to prevent and treat invasive fungal infections. The purpose of this study was to evaluate the pharmacokinetic equivalency of a test formulation and reference formulation (Vfend®) of Voriconazole.
Materials and methods: This was a randomized, open-label, single-dose, two-treatment, two-sequence, two-cycle, crossover phase I trial. The 48 subjects were equally divided into 4 mg/kg and 6 mg/kg groups. Within each group, the subjects were randomized 1:1 to the test or reference formulation.. After a 7-day washout period, crossover formulations were administered. The blood samples were collected at 0.5, 1.0, 1.33,1.42,1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 4 mg/kg group, while at 0.5, 1.0, 1.5, 1.75, 2.0, 2.08, 2.17, 2.33, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0 h later in the 6 mg/kg group. The plasma concentrations of Voriconazole were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The safety of the drug was evaluated.
Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ in both 4 mg/kg and 6 mg/kg groups were within the prespecified bioequivalence limits between 80 ~ 125%. In the 4 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (2.552 ± 0.448) μg/mL, AUC0-t was (11.875 ± 7.157) h*μg/mL and AUC0-∞ was (12.835 ± 9.813) h*μg/mL after a single dose of 4 mg/kg test formulation. The mean Cmax was (2.615 ± 0.464) μg/mL, AUC0-t was (12.500 ± 7.257) h*μg/mL and AUC0-∞ was (13.416 ± 9.485) h*μg/mL after a single dose of 4 mg/kg reference formulation. In the 6 mg/kg groups, 24 subjects were enrolled and completed the study. The mean Cmax was (3.538 ± 0.691) μg/mL, AUC0-t was (24.976 ± 12.364) h*μg/mL and AUC0-∞ was (26.212 ± 14.057) h*μg/mL after a single dose of 6 mg/kg test formulation. The mean Cmax was (3.504 ± 0.667) μg/mL AUC0-t was (24.990 ± 12.455) h*μg/mL and AUC0-∞ was (26.160 ± 13.996) h*μg/mL after a single dose of 6 mg/kg reference formulation. Serious adverse event (SAE) was not observed.
Conclusion: In both 4 mg/kg group and 6 mg/kg group, equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence for both test and reference formulations of Voriconazole.
期刊介绍:
BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.