| Objective: Organize the rabbit tissue cage model, to investigate blood and tissue fluid concentration of levofloxacin (LVFX) or ciprofloxacin (CPLX)in rabbit and calculate the pharmacokinetic parameters after intravenous injection, then provide the basis for the transition of in vitro experiments such as sensitivity test of drug combination,MWS,MPC,inducible resistance,selected resistance of Pseudomonas Aeruginosa to in vivo.Metheds:1. Select 12 healthy New Zealand rabbits, which were randomly divided into A, B groups of six, respectively. Get rid of back hair, a 5cm long of sterile porous, hollow chest drainage tube was implanted into the subcutaneous, and then sutured. Application of 800,000 units of penicillin intramuscularly three days to prevent infection.2 weeks later the surgical wound healing, and 4 to 6 weeks, the hollow tube filled with crystal-clear tissue fluid.2. After 24 hours fasting,10mg/kg of LVFX was injected in the left ear vein in rabbits of group A.5min,10min,20min,30min,45min, 1h,2h,3h,4h,6h,8h after the administration,about 1mL of blood was taken from the right ear vein approximately,placed in a centrifuge tube coated with heparin.And 7.5min,15min,30min,1h,2h,3h,4h,5h,6h,7h,8h after the administration,about 0.5mL tissue fluid was taken from the tissue cage approximately,placed in a centrifuge tube.Centrifugation(5000r/min) for 10 minutes,Remove the supernatant, establishing an HPLC method to determinate the drug concentrations and calculate the pharmacokinetic parameters.The standard curve in plasma:y=0.4042x+0.0012 (r= 0.9992;The standard curve in tissue fluid:y=0.6866x-0.0053 (r= 0.9993)3.2mg/kg of CPFX was injected in the left ear vein in rabbits of group B, and 5 min,10 min,15 min,20 min,30 min,40 min, 1h,1.5h,2h,2.5h,3h after the administration, about 1mL of blood was taken from the right ear vein approximately, placed in a centrifuge tube coated with heparin. And 15min,30min, 1h,1.5h,2h,2.5h, 3h,3.5h,4h,5h,6h after the administration,about 0.5mL tissue fluid was taken from the tissue cage approximately, placed in a centrifuge tube. Centrifugation (5000r/min) for 10 minutes, remove the supernatant, establishing an HPLC method to determinate the drug concentrations and calculate the pharmacokinetic parameters.The standard curve in plasma:y=1.8748x-0.0005 (r= 0.9998);The standard curve in tissue fluid: y=1.4876x+0.0063 (r= 0.9994)Results:1. The drug concentration-time datas were calculated and evaluated with DAS software. Levofloxacin and ciprofloxacin in the blood of rabbits are in line with a two-compartment pharmacokinetic model, and the tissue fluid pharmacokinetics are in line with a one-compartment model.2. The peak concentrations (Cmax) of LVFX in blood and tissue fluid were (8.27±0.9), (2.48±0.3)mg/L respectively; The peak time(Tmax) were(0.017±0.1) h, (2.48±0.3) h;The half-life(T1/2β) were (1.06±0.1),(3.63±1.3)h; The clearance(CL) in blood and tissue fluid were (0.96±1.3), (0.96±0.1) L/h/kg; The apparent volume of distribution(V) were (1.55±0.3), (4.89±2.1) L/kg, respectively; Area under the concentration-time curve [AUC(0-t)] were (9.68±1.4) mg·L-1·h, (8.88±1.6) mg·L-1·h;[AUC(0-∞)] were (9.82±1.4) mg·L-1·h, (11.0±1.4) mg·L-1·h.3. The peak concentrations (Cmax) of CPFX in blood and tissue fluid were (2.68±0.3), (3.35±0.8) mg/L,respectively;The peak time (Tmax) were (0.1±0.0), (0.75±0.5) h;The half-life (T1/2β)were (1.13±0.1)h,(1.56±0.7)h; The clearance in blood and tissue fluid were (0.90±0.2), (0.24±0.1) L/h/kg;The apparent volume of distribution(V)were (1.35±0.5), (0.50±0.2) L/kg, respectively; Area under the concentration-time curve [AUC(0-t)] were (2.29±0.7) mg·L-1·h, (8.34±1.1) mg·L-1·h;[AUC(0-∞)] were (2.42±0.7) mg·L-1·h, (9.14±0.7) mg·L-1·h。Discussion:1. It is about 2 hours after intravenous administration of LVFX that the drug in the tissue fluid reached a peak concentration(Cmax),and it can keep more than 8 hours. Compared with plasma, the peak time (Tmax) of drug in the tissue fluid delayed, but the half-life(T1/2β) is longer, which declared LVFX administered 2 times a day we can control the bacterial infection in the tissue fluid.2. It is about 45 minutes after intravenous administration of CPFX that the drug in the tissue fluid reached a peak concentration(Cmax), the Cmax of tissue fluid and blood are similar, the half-life (T1/2β) is longer, but it is shorter in rabbits than in humans, so if we want to control the bacterial infection in the tissue fluid, we need to increase the number of drug delivery.3. The penetration of fluoroquinolones such as LVFX and CPFX are strong, the fluctuation of drug concentration is small,which can form an effective antibiotic barrier in the rabbit tissue cage,continue to act the antibacterial effect and can be used in the study of the treatment of pathogen infection.4. The main advantage of the rabbit cage model is to complete the pharmacokinetic process at the same rabbits, which is commonly used in the determination of tissue distribution of drugs and other researchs. The pharmacokinetic parameters can be used to design the rational dosage regimen in rabbits, then provide the basis for the transition of in vitro experiments such as sensitivity test of drug combination, MWS, MPC, inducible resistance, selected resistance of Pseudomonas Aeruginosa to in vivo.
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