Satterwhite J H, Cerimele B J, Coleman D L, Hatcher B L, Kisicki J, DeSante K A
Lilly Research Laboratories, Wishard Memorial Hospital, Indianapolis, Indiana 46202.
Postgrad Med J. 1992;68 Suppl 3:S3-9.
The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2-receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine.
在两项研究中对头孢克洛新型制剂（头孢克洛AF）的药代动力学和生物利用度进行了研究，一项研究比较了健康的老年和年轻志愿者，另一项研究评估了抗酸剂和H2受体拮抗剂对头孢克洛AF生物利用度的影响。对30名年龄在65至84岁之间的受试者和10名年龄在21至45岁之间的对照受试者研究了750mg剂量头孢克洛AF的药代动力学。与对照组相比，老年受试者的头孢克洛血浆浓度较高，这归因于较低的血浆清除率。年龄与肾功能之间存在很强的关联，头孢克洛的血浆清除率高度依赖于肾功能。因此，肾功能受损的老年患者消除头孢克洛的能力降低。由于消除半衰期短且治疗指数宽，中度肾功能不全的患者无需调整剂量。第二项试验中的15名健康男性交叉接受了五种治疗，包括单独使用头孢克洛AF（500mg）、在使用头孢克洛AF之前或之后使用西咪替丁、在使用头孢克洛AF之后使用氢氧化铝镁片TC以及单独使用速释头孢克洛（500mg）。头孢克洛AF和速释头孢克洛具有相似的生物利用度，但服用头孢克洛AF时血浆浓度维持的时间更长。西咪替丁没有改变头孢克洛AF的生物利用度，但与头孢克洛AF共同给药的氢氧化铝镁片TC降低了吸收程度。这表明头孢克洛AF的生物利用度受抗酸剂氢氧化铝镁片TC的影响，但不受H2受体拮抗剂西咪替丁的影响。
