BackgroundDicloxacillin, 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.MethodsA 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.ResultsFollowing 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.ConclusionDicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10 h values.

In healthy Chinese subjects, single dosing of sitafloxacin resulted in linear plasma pharmacokinetics.

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A highly sensitive, simple, and rapid liquid chromatography tandem mass spectrometry method to simultaneously determine blonanserin and blonanserin C in human plasma with AD-5332 as internal standard (IS) was established. A simple direct protein precipitation method was used for the sample pretreatment, and chromatographic separation was performed on a Waters XBridge C8 (4.6 × 150 mm, 3.5 μm) column. The mobile phase consists of a mixture of 10 mM ammonium formate and 0.1% formic acid in water (A) and 0.1% formic acid in methanol (B). To quantify blonanserin, blonanserin C, and IS, multiple reaction monitoring (MRM) was performed in positive ESI mode. The calibration curve was linear in the concentration range of 0.012–5.78 ng·mL−1 for blonanserin and 0.023–11.57 ng·mL−1 for blonanserin C (r 2 > 0.9990). The intra- and interday precision of three quality control (QC) levels in plasma were less than 7.5%. Finally, the current simple, sensitive, and accurate LC-MS/MS method was successfully applied to investigate the pharmacokinetics of blonanserin and blonanserin C in healthy Chinese volunteers.

Background and ObjectivesCefozopran is a parenteral cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The objective of this study was to evaluate the pharmacokinetics of cefozopran after single- and multiple-dose intravenous administration in healthy subjects, to provide clinical guidance in its application.MethodsThis was a single-center, open-label, randomized, two-phase study conducted in 12 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.5, 1.0 and 2.0 g of injected cefozopran hydrochloride in a three-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects received 2.0 g every 12 h for 4 days. 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.ResultsTwelve healthy volunteers (six males and six females) were enrolled and completed the study. Following a single 1-h intravenous infusion of 0.5, 1.0 or 2.0 g cefozopran, maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUClast) increased in a dose-proportional manner. The mean half-life in plasma (t½) was in the range of 1.20–2.80 h. Cefozopran was mainly excreted in its unchanged form, with no tendency for accumulation, via the kidney, and varied from 65.99 to 73.33 %. No appreciable accumulation of either drug occurred with multiple intravenous doses of cefozopran, and pharmacokinetic parameters for cefozopran were similar on days 1 and 4. No serious adverse events were reported. Adverse events were generally mild.ConclusionCefozopran was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUClast values.