Hill S L, Bilton D, Johnson M M, Pye A, Mitchell J L, Stockley R A
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham, UK.
J Antimicrob Chemother. 1994 Jan;33(1):129-36. doi: 10.1093/jac/33.1.129.
Sputum and serum pharmacokinetics of loracarbef (LY163892) were performed in 19 patients with purulent bronchiectasis. Nine of the patients received 200 mg twice daily and ten patients, 400 mg twice daily, for a total of 14 days. beta-Lactamase activity was measurable in the lung secretions of all 19 patients at the start of therapy. Mean peak serum concentrations of 11.7 mg/L (S.E.M. 1.7) were recorded at 1 h after administration of 200 mg doses on day 2 of therapy and were 18.5 mg/L (S.E.M. 1.9) at 1.5 h in the 400 mg group. Loracarbef was shown to penetrate lung secretions even in the presence of beta-lactamase activity. Mean peak sputum concentrations were achieved between 2 and 4 h following dosing and were 0.2 mg/L (S.E.M. 0.05) in the 200 mg group and 0.4 mg/L (S.E.M. 0.08) in the 400 mg group. On days 7 and 14 of therapy, sputum loracarbef concentrations were similar 4 h after the morning dose (0.23 mg/L following 200 mg; 0.35 mg/L after 400 mg). These concentrations were approximately 2% of the peak serum concentration and penetration into lung secretions is similar to other beta-lactams.
对19例化脓性支气管扩张患者进行了氯碳头孢（LY163892）的痰液和血清药代动力学研究。9例患者每日两次服用200mg，10例患者每日两次服用400mg，共治疗14天。治疗开始时，所有19例患者的肺分泌物中均可检测到β-内酰胺酶活性。治疗第2天，服用200mg剂量后1小时记录的血清平均峰值浓度为11.7mg/L（标准误1.7），400mg组在1.5小时时为18.5mg/L（标准误1.9）。即使存在β-内酰胺酶活性，氯碳头孢仍能穿透肺分泌物。给药后2至4小时达到痰液平均峰值浓度，200mg组为0.2mg/L（标准误0.05），400mg组为0.4mg/L（标准误0.08）。在治疗的第7天和第14天，早晨给药后4小时痰液中氯碳头孢浓度相似（200mg后为0.23mg/L；400mg后为0.35mg/L）。这些浓度约为血清峰值浓度的2%，其进入肺分泌物的情况与其他β-内酰胺类药物相似。
