[Toxicokinetics of paraquat in rabbits].
OBJECTIVE
to develop a high performance liquid chromatography method (HPLC) for the determination of paraquat in rabbit plasma and study its toxicokinetics in rabbits.


METHODS
twelve rabbits were randomly divided into 2 groups with giving oral and intravenous administration of paraquat at a single dose of 60 mg/kg and 6 mg/kg respectively. The plasma paraquat concentrations were determined by HPLC and calculated by DAS pharmacokinetics program.


RESULTS
the linear range of paraquat in plasma was 0.05 ∼ 50.00 mg/L (r = 0.9998). The relative recoveries of the assay were 99.41% ∼ 102.32%. The absolute recoveries of the assay were 83.72% ∼ 90.48%. Both the intra-day and inter-day validations were less than 10%. For oral administration, the toxicokinetics parameters of paraquat were as follows: Cmax (14.46 ± 2.35) mg/L, Tmax (1.63 ± 0.31) h, AUC(0-t) (177.61 ± 14.62) mg × h/L, AUC(0-∞) (182.24 ± 14.54) mg × h/L, While for intravenous administration, the toxicokinetics parameters of paraquat: Cmax (35.13 ± 5.53) mg/L, Tmax 0.05 h, AUC(0-t) (121.74 ± 12.30) mg × h/L, AUC(0-∞) (125.12 ± 12.17) mg × h/L, The difference of these parameters between the two groups had statistical significance (P < 0.05). The oral bioavailability was (14.66 ± 1.55)%.


CONCLUSIONS
the oral bioavailability of paraquat is relatively low. The biological half life of paraquat is relatively long and there is no significant difference between oral administration and intravenous on biological half life. This method is simple, sensitive and accurate. It can be used for the investigation of paraquat in rabbits.
Department of Pharmacology, Wenzhou Medical College, Wenzhou 325000, China.
Xin
X
Kan
Xiao-Yun
XY
Zhang
Jie
J
Dong
Wan-Shu
WS
Li
Guo-Xin
GX
Hu
Zhong-Qiu
ZQ
Lu
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D008297:Male; D010269:Paraquat / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D011817:Rabbits
D010269:Paraquat