Research On Pharmacokinetics Of Sparfloxacin For Oral Administration

OBJECTIVES:To explore a High Performance Liquid Chromatogra -phy (HPLC) method for the analysis of Sparfloxacin in biological samples. To study the pharmacokinetics(PK) of sparfloxacin after oral administration in rabbits.To study the distribution and pharmacokinetics of sparfloxacin in ocular tissues after oral administration in rabbits .To study bivequivalence of two kinds of sparfloxacin capsule.And get the plasma protein binding rate of SPFX. All of the researches will provide data for clinic prescription.METHODS:(1)The analysis method of SPFX:The SPFX in biological samples were liquid liquid extraction (LLE) with dichlormethane. SPFX was separated on the Gemini Cl8 250mm×4.6mm,5μm column using potassium dihydrogen phosphate--triethylamine--methanol as the moblie phase(flow rate 1.2mL·min-1) and GFLX as the internal standard at 30℃with UV detector at wavelength 292nm. (2)Plasma samples were taken in different times after oral administration in 6 rabbits with 12.4mg·kg-1.The concentrations of the sparfloxacin were determined in plasma by HPLC . The pharmacokinetics parameters were calculated by 3p97.(3) Ocular tissues samples were taken in different times after oral administration in 27 rabbits with 12.4mg·kg-1.The concentrations of sparfloxacin in lacrimal fluid,cornea,aqueous humor,iris-ciliary body,lens and vitreous body were determined by HPLC. The pharmacokinetics parameters were calculated by 3p97.(4)A single dose of 200mg of sparfloxacin capsule was administered by randomized crossover way in 22 volunteers and the plasma concentrations of the sparfloxacin were determined by HPLC . The pharmacokinetic parameters were calculated with 3P97.Bivequivalence was evaluated . (5)The equilibrium dialysis combined with HPLC to determine the plasma concentration and plasma protein binding rate of SPFX was carried out.RESULTS:The concentration-time curve of sparfloxacin fitted two compartment model. The peak plasma levels(Cmax) was(4.79±0.39)μg·mL- 1 ;the peak time(tmax) was (3.80±0.45)h; A UC0～t was (113.65±10.81)μg·h·mL- 1. The peak concentration of sparfloxacin in lacrimal fluid ,cornea, a queous humor ,i ris-ciliary body, l ens and vitreous body was (13.75±1.36)μg·mL - 1, (3.25±0.32)μg·g - 1, (2.06±0.14)μg·mL- 1,(3.41±0.26)μg·g -1 ,( 1.62±0.13)μg·g - 1,( 2.18±0.18)μg·mL- 1respectively;the half-life time in various tissues was (8.18±0.70)h ,( 9.94±3.90)h ,(5.05±0.66)h ,( 13.54±6.37)h, ( 5.67±1.15)h, ( 3.60±1.23)h respectively ;A UC0～t in various tissues was (118.68±5.64)μg·h·mL- 1 , (28.18±5.42)μg·h·g - 1,(17.52±2.09)μg·h·mL - 1,( 36.77±10.47)μg·h·g - 1, (16.12±0.59)μg·h·g- 1, (16.57±0.47)μg·h·mL- 1 respectively.The concentration-time curves of two preparations fitted two compartment model . The peak plasma levels (Cmax) were(0.85±0.23)μg·mL-1 and(0.90±0.27)μg·mL-1, respectively. The peak time(tmax) were(5.59±2.28)h and(4.95±1.17)h,respectively . AUC0～t were (27.92±6.09)μg·h·mL- 1 and (29.65±8.49)μg·h·mL- 1 ,respectively . The relative bioavailabitity of sparfloxacin capsule was (97.47±18.32)%.The plasma protein binding rates of SPFX at low,middle and high concentrations were 45.12% ,45.52% and 45.50% respectively.Conclusion:The method for the determination of SPFX in biological samples was sensitive,simple,rapid and good reproduction.It can be used to determine the concentration of SPFX in the biological samples and study the pharmacokinetics(PK) parameters of it.Sparfloxacin has a high concentration in blood of rabbits after oral administration. The half time is long.SPFX has a good distribution and high concentration in various intraocular tissues of rabbit after oarl administration. It can replace parenteral sparfloxacin for ophthalmic diseases.The result of two one-sided t tests ( P> 0.05 )suggest that the test is bivequivalence with the reference.SPFX has high binding power with plasma protein.