title: The pharmacokinetics change of cefepime after Shuanghuanglian injection administration in subjects with the renal damage.
abstract: Shuanghuanglian injection (SHLI) has been widely used for administration with cephalosporin in China for long time. The objective of this study was to evaluate the pharmacological properties and biochemical changes of cefepime combined with SHLI. The SD rats included were received either an intravenous (iv. 4 mL/kg) dose of normal saline, or intravenous (iv. 0.74, 0.37, 0.185 g/kg, respectively) doses of SHLI once daily for 7 days. After last administration, cefepime (0.41 g/kg) was intravenous injected to the animals. The serum and urine samples were acquired and stored at 4 °C. They were used for quantitative determination of urea nitrogen (BUN), creatinine (CRE), urine protein, alkaline phosphatase (ALP) and N-acetyl-B-d-glucosaminidase (NAG). At different time points, the levels of cefepime in rat plasma were estimated for pharmacokinetic measures by HPLC. Aspirin was selected as internal standard (IS). The results showed that there were positive effects by increasing the total amount of CRE, BUN, NAG and urine protein (p < 0.01 or <0.05) and decreasing the levels of ALP (especially the high dose group of SHLI with cefepime) (p < 0.01). Besides, the pharmacokinetic results indicated that cefepime was distributed as non-compartment model after intravenous administration. Compared with the corresponding values for the compounds given alone, the area under the blood drug concentration time curve (AUC0-t and AUC0-∞) was better increased in middle- and high-dose groups (pall < 0.01), the mean residence time (MRT) of cefepime was larger (pall < 0.01) and the total clearance (CL) was lower at different levels. The results mean that the duration and concentration of cefepime could be prolonged and the clearance reduced while in combination with SHLI. Furthermore, the cefepime in the three tested doses caused changes of renal tubular epithelial cells while the severity of changes mainly dependent on the specific doses. In conclusion, the results above-mentioned suggest a possible contribution of drug combination in the nephrotoxicity and biochemical alterations especially at high doses. Further, monitoring measures for the renal functions are warranted to evaluate during the combination of these two drugs.
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Min
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Weirong
authors.initials: W
authors.lastname: Li
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Suiqing
authors.initials: S
authors.lastname: Mi
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Ningsheng
authors.initials: N
authors.lastname: Wang
authors.affiliation: a Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine , Guangzhou , Guangdong Province , PR China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000652:urine*; D019540:Area Under Curve; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D057230:Limit of Detection; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004365:Drugs, Chinese Herbal; C516400:shuang-huang-lian; D000077723:Cefepime
keywords: Cefepime; Shuanghuanglian injection; combination; nephrotoxicity