Etimicin-loaded bone cement implants: pharmacokinetics and nephrotoxicity in rabbits
- Author:
Lu MAO
1
,
2
Author Information
- Publication Type:Journal Article
- Keywords: Antibacterial drugs; Bone cement; Clinical safety; Etimicin; Release
- From: Chinese Pharmaceutical Journal 2015;50(18):1619-1623
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To investigate the local release and blood levels of etimicin from etimicin-loaded bone cement (ELBC) implants and their nephrotoxicity in rabbits. METHODS: Handmade cylindrical ELBC implants were quantitatively prepared and surgically implanted in rabbit femoral medullary cavity. The drug concentrations in local bone and surrounding tissues were determined. Blood levels of drug released from ELBC implants were determined at different time intervals post-implantation. The pharmacokinetic parameters of ELBC implants were calculated by using Phoenix WinNonlin 6.3 software. Blood urea nitrogen and serum creatinine in rabbits were determined using automatic biochemistry analyzer before and after drug administration to assess the nephrotoxicity. RESULTS: The major pharmacokinetic parameters of ELBC implants were as follows; t1/2 (13.2±4.71) h; tmax (4.44±0.88) h; ρmax (7163.153±1673.618) ng·mL-1. The drug concentrations of ELBC implants in local bone marrow were (226.14±60.20), (16.00±11.40), and (5.98±1.97) μg·g-1 after implantation for 1, 2, and 4 weeks, respectively. The corresponding concentrations of drug in the cortex of bone tissues were (54.68±36.98), (3.95±1.73), and (1.39±0.77) μg·g-1, respectively. The levels of blood urea nitrogen and serum creatinine had no significant change after the treatment of ELBC implants. CONCLUSION: Compared with intramuscular injection, ELBC implants result in sustained drug release, maintain drug concentration in local tissues higher than the minimum inhibitory concentration against most infectious bacteria for at least one month, and display lower nephrotoxicity, indicating a good prospect for clinical use.
