Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses
Guolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangz...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-10-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | https://www.dovepress.com/safety-and-pharmacokinetics-of-dicloxacillin-in-healthy-chinese-volunt-peer-reviewed-article-DDDT |
| _version_ | 1831689101472956416 |
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| author | Wu GL Zheng YL Zhou HL Hu XJ Liu J Zhai Y Zhu MX Wu LH Shentu JZ |
| author_facet | Wu GL Zheng YL Zhou HL Hu XJ Liu J Zhai Y Zhu MX Wu LH Shentu JZ |
| author_sort | Wu GL |
| collection | DOAJ |
| description | Guolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Background: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers.Methods: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.Results: Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration–time curve from 0 to 10 hours (AUC0–10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild.Conclusion: Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10 h values. Keywords: dicloxacillin, safety, tolerability, pharmacokinetics, healthy volunteers |
| first_indexed | 2024-12-20T10:43:26Z |
| format | Article |
| id | doaj.art-bbaf8c90c573426db5043efd1e401a10 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-20T10:43:26Z |
| publishDate | 2015-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-bbaf8c90c573426db5043efd1e401a102022-12-21T19:43:30ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-10-012015default5687569524186Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral dosesWu GLZheng YLZhou HLHu XJLiu JZhai YZhu MXWu LHShentu JZGuolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Background: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers.Methods: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.Results: Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration–time curve from 0 to 10 hours (AUC0–10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild.Conclusion: Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10 h values. Keywords: dicloxacillin, safety, tolerability, pharmacokinetics, healthy volunteers https://www.dovepress.com/safety-and-pharmacokinetics-of-dicloxacillin-in-healthy-chinese-volunt-peer-reviewed-article-DDDT |
| spellingShingle | Wu GL Zheng YL Zhou HL Hu XJ Liu J Zhai Y Zhu MX Wu LH Shentu JZ Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses Drug Design, Development and Therapy |
| title | Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses |
| title_full | Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses |
| title_fullStr | Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses |
| title_full_unstemmed | Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses |
| title_short | Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses |
| title_sort | safety and pharmacokinetics of dicloxacillin in healthy chinese volunteers following single and multiple oral doses |
| url | https://www.dovepress.com/safety-and-pharmacokinetics-of-dicloxacillin-in-healthy-chinese-volunt-peer-reviewed-article-DDDT |
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