比阿培南在连续性肾替代治疗患者中的药动学研究

Pharmacokinetics of Biapenem During in Patients with Continuous Renal Replacement Therapy

关键词:  比阿培南  连续性肾脏替代治疗  血药浓度  药动学

Key words:  biapenem  continuous renal replacement therapy  blood concentration  pharmacokinetics

摘要:

目的 建立HPLC检测血浆和置换液中比阿培南的方法，研究患者在接受连续性肾替代治疗（continuous renal replacement therapy，CRRT）时比阿培南的药动学。方法 色谱柱采用ZORBAX Eclipse XDB-C₁₈（4.6 mm×150 mm，5 μm）；以甲醇（A）-0.1 mmol·L^-1醋酸钠溶液（B）（0~6.5 min，2%A；6.5~7 min，2%→60%A；7~15 min，60%A）为流动相，检测波长为300 nm，内标为卡马西平，流速为1.0 mL·min^-1。10名接受CRRT治疗的患者静脉30 min匀速滴注比阿培南0.3 g。均于给药前及给药后0，5，15，30，45 min和1，2，4，6，8 h采集滤器前的血液和置换液进行检测。结果 血浆和置换液中比阿培南的浓度在0.2~50μg·mL^-1内线性关系良好；高中低3个浓度的血浆和置换液样品平均回收率分别为（101.05±4.31）%和（101.09±2.72）%，日内、日间RSD均<5%，接受CRRT治疗时比阿培南的药动学以二室模型描述最佳，C_max为（15.37±2.98）mg·L^-1、t_1/2β为（71.36±40.41）min、V₁为（11.75±3.86）L、AUC_0-∞为（0.64±0.15）mg·L^-1·min^-1。结论 本研究建立的HPLC灵敏度高、稳定性好、选择性强以及精密度高，比阿培南在接受CRRT治疗时药动学未见明显改变。

Abstract:

OBJECTIVE To establish HPLC method in the detection of plasma and displacement liquid of biapenem and to study pharmacokinetics of biapenem in the patients with continuous renal replacement therapy. METHODS HPLC column was ZORBAX Eclipse XDB-C₁₈(4.6 mm×150 mm, 5 μm)with the mobile phase of methanol(A)-0.1 mmol·L^-1sodium acetate solution(B)(0-6.5 min, 2%A; 6.5-7 min, 2%→60%A; 7-15 min, 60%A). The wavelength of detection was 300 nm. The internal standard was carbamazepine and the flow rate was 1.0 mL·min^-1. Ten cases of CRRT patients were given 0.3 g dose of biapenem with iv. 2 mL venous blood was collected after giving medicine at 0, 5, 15, 30, 45 min and 1, 2, 4, 6, 8 h, while 2 mL displacement liquid were collected. RESULTS Displacement liquid and plasma concetration of biapenem had a good linear relation in the range of 0.2-50 μg·mL^-1. The three different concentration(low, medium and high) plasma and displacement liquid sample's average recovery were (101.05±4.31)% and(101.09±2.72)%. The intra-and inter-day precision was both < 5%. The pharmacokinetics of biapenem best fitted to two-compartment model:C_max was (15.37±2.98)mg·L^-1;t_1/2β was (71.36±40.41)min, V₁ was (11.75±3.86)L, AUC_0-∞ was (0.64±0.15) mg·L^-1·min^-1. CONCLUSION The method of HPLC has the features of high sensitivity, excellent stability, strong selectivity and high precision. There is no obvious change on pharmacokinetics of biapenem in the patients with CRRT.