Study On Effect Of Platycodon Grandiflorum On Pharmacokinetics Of Florfenicol And Distribution In Tissues In New Zealand White Rabbits After Oral And Intramuscular Administration

Objectives: To study the effect of platycodon grandiflorum on pharmacokinetics of Florfenicol and distribution in tissues in New-Zealand rabbits after oral and intramuscular administration.Procedures: In the first part ,40 healthy rabbits were allocated into four groups(groupA, B, C, D); In the second part ,80 healthy rabbits were divided into four groups(groupA, B, C, D).The rabbits in Group A were given an oral dose of 30 mg of Florfenicol /kg; The rabbits in Group B were given an intramuscular dose of 30 mg of Florfenicol /kg; The rabbits in Group C were given an oral dose of 30 mg of Florfenicol /kg and 2 g of platycodon grandiflorum /kg simultaneously; The rabbits in Group D were given an intramuscular dose of 30 mg of Florfenicol /kg and an oral dose of 2 g of platycodon grandiflorum /kg simultaneously. The congcentration of Florfenicol in plasma and tissues(including heart,lung,liver,kidney) were drtermined by HPLC with a limit of detection of 0.05 mg/L in plasma and 0.25μg/g in tissues,respectively. Pharmacokinetics parameters were evaluated by 3P97 pharmacokinetics programme. Parameters were analyzed by SPSS (12.0) software..Results:The Model were fitted a one-compartment Model with 1st Order Absorption(weight=1/C²).The main pharmacokinetics parameters and calculated-equations in rabbits were as follows,respectively: Group A: T_1/2Ka0.461±0.066h, T_1/2ke2.013±0.195h , _Tpeak1.180±0.123h , C_max7.332±1.000mg·L^-1 , AUC31.445±3.566mg · h·L^-1 , V/F2.995±0.330 L·kg^-1, C=19.833(e^-0.396t-e^-2.387t); Group B: T_1/2Ka0.802±0.098h, T_1/2ke2.317±0.136h , T_peak1.805±0.103h , C_max6.646±0.578mg·L^-1, AUC38.714±3.727mg· h·L^-1 , V/F2.772±0.303L·kg^-1, C=22.106(e^-0.308t-e^-0.994t); Group C: T_1/2Ka0.550±0.112h, T_1/2ke3.308±0.270h , T_peak1.414±0.183h , C_max4.737±0.360mg·L^-1, AUC23.128±2.096mg · h·L^-1 , V/F1.400i0.127 L ·kg^-1, C=11.021(e^-0.342t-e^-1.860t); Group D: T_1/2Ka1.067±0.920h, T_1/2ke2.744±0.379h , T_peak2.301±0.186h , C_max5.287±0.591mg·L^-1, AUC35.232±2.668mg · h·L^-1, V/F3.649±0.755 L ·kg^-1,C=21.642(e^-0.288t-e^-0.691t) .Conclusions:(1)After given Florfenicol and platycodon grandiflorum orally simultaneously, platycodon grandiflorum could influence the pharmacokinetic variables of Florfenicol in healthy rabbits significantly:decreased the speed of absorption;enhanced the distribution;retarded the speed of elimination.After given Florfenicol intramuscularly and platycodon grandiflorum orally simultaneously, platycodon grandiflorum could not influence the pharmacokinetic variables of Florfenicol in healthy rabbits significantly,only decreased the speed of absorption.(2) After given Florfenicol and platycodon grandiflorum orally simultaneously, platycodon grandiflorum Leading action could influence notably the distribution of Florfenicol in tissues: increased the drug concentration and retarded the speed of elimination in heat and lung tissue. After given Florfenicol intramuscularly and platycodon grandiflorum orally simultaneously, platycodon grandiflorum had no effect on the distribution of Florfenicol in tissues,only retarded the speed of absorption.