Borner K, Lode H, Hampel B, Pfeuffer M, Koeppe P
Chemotherapy. 1985;31(4):237-45. doi: 10.1159/000238342.
The pharmacokinetics of ceftriaxone (CRO) after subcutaneous and intravenous administration was studied in 10 healthy volunteers (5 males, 5 females, age 22-43 years, body weight 64.3 +/- 9.5 kg). Each of them received 2.0 g CRO i.v., and then 0.5 g i.v. and 0.5 g CRO s.c. in a randomized cross-over design. Subcutaneous administration of ceftriaxone was tolerable in combination with lidocaine. Serum and urine concentrations were determined by high performance liquid chromatography and for comparison with a bioassay. Mean serum concentrations were high after intravenous administration: 258 +/- 40 mg/1 (0 min, 2 g i.v.) resp. 84 +/- 40 mg/1 (0 min, 0.5 g i.v.). They declined to 11.6 +/- 4.2 mg/1 (2 g) resp. 6.5 +/- 2.2 mg/1 (0.5 g i.v.) within 24 h. Following subcutaneous application peak serum concentrations of 37.1 +/- 5.6 mg/1 were found after 138 +/- 49 min and a mean serum concentration of 6.6 +/- 1.6 mg/1 after 24 h. Concentrations of free ceftriaxone, determined by ultrafiltration, were 9.2 +/- 2.7% of total concentrations from 25 to 200 mg/1. Cumulated urine recoveries over a period of 24 h were: 51.2 +/- 8.9% (2 g i.v.), 47.1 +/- 7.9% (0.5 g i.v.) and 39.7 +/- 9.5% (0.5 g s.c.). There was no evidence for the presence of a microbiologically active metabolite in urine. Comparison of pharmacokinetic parameters for the 0.5 g dose did not show relevant differences between intravenous and subcutaneous administration (using an open two-compartment model): t beta 1/2 (min) 514 +/- 104 (s.c.), 592 +/- 133 (i.v.), VD,Area (1) 11.9 +/- 3.8 (s.c.), 13.3 +/- 3.8 (i.v.) and AUCtot (mg X h/1) 515 +/- 106 (s.c.) and 549 +/- 125 (i.v.). Bioavailability of the subcutaneous application was 0.96 +/- 0.26. For the 2 g i.v. dose the known nondosis-dependent kinetics was observed. Subcutaneous administration of ceftriaxone appears to be a possible alternative to the intravenous route in selected clinical situations or cases.
在10名健康志愿者（5名男性，5名女性，年龄22 - 43岁，体重64.3±9.5 kg）中研究了头孢曲松（CRO）皮下和静脉给药后的药代动力学。他们每个人接受2.0 g CRO静脉注射，然后采用随机交叉设计接受0.5 g静脉注射和0.5 g CRO皮下注射。头孢曲松与利多卡因联合皮下给药是可耐受的。通过高效液相色谱法测定血清和尿液浓度，并与生物测定法进行比较。静脉给药后平均血清浓度较高：分别为258±40 mg/L（0分钟，2 g静脉注射）和84±40 mg/L（0分钟，0.5 g静脉注射）。在24小时内它们分别降至11.6±4.2 mg/L（2 g）和6.5±2.2 mg/L（0.5 g静脉注射）。皮下给药后，在138±49分钟时发现血清峰值浓度为37.1±5.6 mg/L，24小时后平均血清浓度为6.6±1.6 mg/L。通过超滤测定的游离头孢曲松浓度为总浓度的9.2±2.7%，范围为25至200 mg/L。24小时内累积尿回收率分别为：51.2±8.9%（2 g静脉注射），47.1±7.9%（0.5 g静脉注射）和39.7±9.5%（0.5 g皮下注射）。尿液中未发现有微生物活性代谢物存在的证据。对于0.5 g剂量，静脉和皮下给药的药代动力学参数比较未显示出相关差异（使用开放二室模型）：tβ1/2（分钟）514±104（皮下），592±133（静脉），VD,Area（L）11.9±3.8（皮下），13.3±3.8（静脉），AUCtot（mg·h/L）515±106（皮下）和549±125（静脉）。皮下给药的生物利用度为0.96±0.26。对于2 g静脉注射剂量，观察到已知的非剂量依赖性动力学。在特定临床情况或病例中，头孢曲松皮下给药似乎是静脉给药途径的一种可能替代方法。
