Wildfeuer A, Laufen H, Leitold M, Zimmermann T
Pfizer/Mack, R & D Laboratories, Illertissen, Germany.
J Antimicrob Chemother. 1993 Jun;31 Suppl E:51-6. doi: 10.1093/jac/31.suppl_e.51.
In an open crossover study, the pharmacokinetics of three-day and five-day regimens of azithromycin were compared. Fourteen healthy volunteers received oral doses of azithromycin once-daily, over three days (500 mg/day) and over five days (500 mg on day 1, followed by 250 mg/day on days 2-5). Plasma and urine concentrations were determined by HPLC. Azithromycin was found to be absorbed rapidly on the first and the last days of both regimens, with mean Tmax ranging between 2.5-3 h. On day 1, peak plasma concentrations were 0.37 mg/L and 0.31 mg/L, respectively, with three- and five-day regimens, and increased to 0.42 mg/L on the last day of the three-day regimen, but decreased to 0.18 mg/L at the end of the five-day regimen. Similarly, the AUC0-24 increased from 1.30 to 1.88 h.mg/L during the three-day regimen, and decreased from 1.24 to 0.80 h.mg/L on the five-day regimen. After absorption, azithromycin was distributed rapidly; the respective half-lives were 2.4 h and 2.2 h with the three-day and five-day regimens. Thereafter, a polyphasic decline of plasma concentrations was observed; the average half-lives between 8-48 h after administration were 27.9 h (three-day regimen) and 35.8 h (five-day regimen). In urine, 5.5% (three-day regimen) and 4.6% (five-day regimen) of the total dose was found as unchanged azithromycin over a 12-day period. The observed pharmacokinetics of azithromycin with both regimens conformed with the known pharmacokinetic behaviour of the drug. The treatment-related differences seen in the plasma concentrations were as expected from the different dosage schedules.
在一项开放性交叉研究中，比较了阿奇霉素三日疗法和五日疗法的药代动力学。14名健康志愿者每日口服一次阿奇霉素，连续服用三天（500毫克/天）和连续服用五天（第1天500毫克，随后第2 - 5天250毫克/天）。通过高效液相色谱法测定血浆和尿液浓度。发现阿奇霉素在两种疗法的第一天和最后一天均迅速吸收，平均达峰时间在2.5 - 3小时之间。在第1天，三日疗法和五日疗法的血浆峰浓度分别为0.37毫克/升和0.31毫克/升，三日疗法在最后一天升至0.42毫克/升，而五日疗法在疗程结束时降至0.18毫克/升。同样，三日疗法期间的AUC0 - 24从1.30小时·毫克/升增至1.88小时·毫克/升，五日疗法则从1.24小时·毫克/升降至0.80小时·毫克/升。吸收后，阿奇霉素迅速分布；三日疗法和五日疗法各自的半衰期分别为2.4小时和2.2小时。此后，观察到血浆浓度呈多相下降；给药后8 - 48小时之间的平均半衰期分别为27.9小时（三日疗法）和35.8小时（五日疗法）。在尿液中，在12天期间，总剂量的5.5%（三日疗法）和4.6%（五日疗法）以未改变的阿奇霉素形式存在。观察到的两种疗法的阿奇霉素药代动力学与该药物已知的药代动力学行为相符。血浆浓度中观察到的与治疗相关的差异与不同给药方案预期的一致。
