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      Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

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          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.


          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.


          Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (C max) 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 (t 1/2) 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.


          Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the C max and AUC 0–10 h values.

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              Minimum inhibitory and bactericidal concentrations of 44 antimicrobial agents against three standard control strains in broth with and without human serum.

              Standard minimum inhibitory and bactericidal concentrations are not established for most antimicrobial agents against strains of bacteria commonly used for quality control in susceptibility testing. The effects of cation and human serum supplementation of broth on the values are also unknown. Therefore, we performed 10 minimum inhibitory and bactericidal concentration determinations for 44 antimicrobial agents against the standard control strains Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853 in Mueller-Hinton broth and in Mueller-Hinton broth supplemented with calcium, magnesium, and 50% pooled human serum. Agreement of replicates was within one twofold dilution 97% of the time. Supplemented Mueller-Hinton broth gave higher minimum inhibitory concentrations for 24 antibiotics against S. aureus, for 17 drugs against E. coli, and for 12 drugs against P. aeruginosa, whereas it gave lower minimum inhibitory concentrations for 1 antibiotic against S. aureus, for 5 against E. coli, and for 5 against P. aeruginosa. Results for minimum bactericidal concentrations were similar. Added serum did not further affect the increased resistance of P. Aeruginosa to aminoglycosides encountered with cation supplementation of broth. These results provide expected values for the quality control strains when minimum inhibitory and bactericidal concentrations are determined in these two Mueller-Hinton media.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                16 October 2015
                : 9
                : 5687-5695
                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
                Author notes
                Correspondence: 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, No 79 Qingchun Road, Hangzhou 310003, People’s Republic of China, Tel +86 571 8723 6560, Fax +86 571 8721 4223, Email stjz@ 123456zju.edu.cn
                © 2015 Wu et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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