Pharmacokinetics Of Doxycycline Hydrochloride Injection In Rabbit

The pharmacokinetics of doxycycline were investigated in rabbits following single intravenous (20mg/kg b.w.), and intramuscular (20mg/kg b.w.) administration of doxycycline hydrochloride injection. Twelve rabbits were used in pharmacokinetics study, and randomly divided into two groups by cross-over design. Blood samples were obtained at different time intervals after administration respectively. The concentration of doxycycline in plasma were determined by reverse high performance liquid chromatography (HPLC). Working conditions of HPLC were as follows: mobile phase was acetonitrile-oxalic acid (34:66), flow rate was 0.8 ml/min, column temperature was 30℃, detection wavelength was 347 nm.Under given chromatography conditions, the concentration of doxycycline in rabbits plasma showed a good liner coefficient relation (R2=0.9999) within the range of 0.0625~64 mg/l. The recoveries were 86.22%~96.12%. The within-day CV and between-day CV were 2.92%~4.14% and 2.48%~5.14% respectively. Limit of detection was 0.02 mg/l, and Limit of quantitation was 0.0625 mg/l.The concentration-time date of doxycycline in plasma were analyzed by 3p87 computer program. The concentration-time date of doxycycline in plasma fitted to a two-compartment open model after single intravenous administration in rabbit. The main pharmacokinetic parameters of doxycycline were as follows: t1/2α: (0.62±0.04) h, t1/2β: (4.76±2.90)h, AUC: (32.54±0.24)mg/l·h, V(c) :(0.63±0.09)l/kg, CL(s): (0.41±0.10) l/kg/h.The concentration-time date of doxycycline in plasma fitted to a two-compartment open model with first-order absorption after single intramuscular administration in rabbit. The main pharmacokinetic parameters were as follows: t1/2ka: (0.16±0.05) h, t1/2α: (2.04±0.24) h, t1/2β:(15.04±5.40) h, T(peak): (0.68±0.12) h, C(max): (1.39±0.07)mg/l, AUC : (10.47±1.15) mg/l·h, F (32.31±0.04) %.The above results showed that the doxycycline hydrochloride injection absorbed slowly, distributed widely, dand eliminated slowly, but had a low bioavailability in rabbit. The doxycycline hydrochloride injection could be injected at the dose of 20mg/kg b.w. once every day in the treatment of infectious diseases caused by sensitive bacterial in rabbit.