Stenquist M, Olen L, Jannert M, Näslund L, Zeckel M L
Department of Oto-Rhino-Laryngology, Akademiska Hospital, Uppsala, Sweden.
Clin Ther. 1996 Mar-Apr;18(2):273-84. doi: 10.1016/s0149-2918(96)80008-7.
Loracarbef, a beta-lactam antibiotic of the carbacephem class, is active in vitro against pathogens associated with acute maxillary sinusitis. To study the extent and duration of maxillary sinus fluid penetration after administration of loracarbef, 20 patients (10 men, 10 women; average age, 41 +/- 13 years) with acute sinusitis were treated with loracarbef 400 mg every 12 hours for 10 days. A lavage catheter was inserted into the maxillary sinus, and 150-microL sinus fluid samples were obtained at 0 (baseline), 0.5, 1, 1.5, 2, and 2.5 hours after the first dose and at 24 and 48 hours (12 hours after the second and fourth doses, respectively). Venous blood samples were obtained at the same times. Maxillary fluid and serum samples were frozen immediately at -20 degrees C to -70 degrees C until later bioassay using a direct agar diffusion method. Excluding missing data or inappropriately timed samples, the mean (+/- SD) sinus fluid concentrations were 0.16 +/- 0.12 microgram/mL at baseline, 0.23 +/- 0.17 microgram/mL at 0.5 hour, 1.11 +/- 1.44 micrograms/mL at 1 hour, 1.63 +/- 2.07 micrograms/mL at 1.5 hours, 1.75 +/- 2.01 micrograms/mL at 2 hours, and 1.60 +/- 1.96 micrograms/mL at 2.5 hours after dose. The mean sinus fluid concentration before the third dose (approximately 12 hours after the second dose) was 1.01 +/- 0.89 microgram/mL and before the fifth dose (approximately 12 hours after the fourth dose) was 0.88 +/- 0.90 microgram/mL. Taking the highest sinus fluid concentration measured in each patient, the mean peak sinus fluid concentration was 2.12 +/- 1.98 micrograms/mL (range, 0 to 6.7 micrograms/mL). The pretherapy peripheral leukocyte count appeared to have a statistically significant association (P < 0.01) with loracarbef sinus fluid penetration as estimated by the sinus fluid area under the concentration-time curve at 0 to 2.5 hours. Loracarbef 400 mg twice daily achieved sinus fluid concentrations that appeared to exceed the minimum concentration required to inhibit 90% of relevant acute sinusitis pathogens throughout the 12-hour interdose interval in most patients with acute maxillary sinusitis.
氯碳头孢是一种碳头孢烯类β-内酰胺抗生素，在体外对与急性上颌窦炎相关的病原体具有活性。为了研究氯碳头孢给药后上颌窦液渗透的程度和持续时间，20例急性鼻窦炎患者（10名男性，10名女性；平均年龄41±13岁）接受氯碳头孢治疗，每12小时400mg，共10天。将冲洗导管插入上颌窦，在首剂后0（基线）、0.5、1、1.5、2和2.5小时以及24和48小时（分别在第二剂和第四剂后12小时）采集150μL的窦液样本。在相同时间采集静脉血样本。上颌窦液和血清样本立即在-20℃至-70℃冷冻，直至后来使用直接琼脂扩散法进行生物测定。排除缺失数据或采样时间不当的样本后，平均（±标准差）窦液浓度在基线时为0.16±0.12μg/mL，0.5小时时为0.23±0.17μg/mL，1小时时为1.11±1.44μg/mL，1.5小时时为1.63±2.07μg/mL，2小时时为1.75±2.01μg/mL，给药后2.5小时时为1.60±1.96μg/mL。第三剂前（约在第二剂后12小时）的平均窦液浓度为1.01±0.89μg/mL，第五剂前（约在第四剂后12小时）的平均窦液浓度为0.88±0.90μg/mL。以每位患者测量的最高窦液浓度计算，平均窦液峰值浓度为2.12±1.98μg/mL（范围为0至6.7μg/mL）。根据0至2.5小时浓度-时间曲线下的窦液面积估计，治疗前外周白细胞计数与氯碳头孢的窦液渗透似乎具有统计学显著相关性（P<0.01）。对于大多数急性上颌窦炎患者，每日两次服用400mg氯碳头孢所达到的窦液浓度在整个12小时的给药间隔内似乎超过了抑制90%相关急性鼻窦炎病原体所需的最低浓度。
