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Study on Pharmacokinetics and Residues of Pyrimethamine in Eel

Author: WuXiaoPing
Tutor: LongLiangQi
School: Huazhong Agricultural University
Course: Hydrobiology
Keywords: Pyrimethamine Pharmacokinetics Residue RP-HPLC Eel (Anguilla japonica)
CLC: S948
Type: Master's thesis
Year: 2008
Downloads: 58
Quote: 0
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Abstract


Pharmacokinetics of Pyrimethamine(PYR) was investigated,following single oral administration at dose of 50mg per kg body weight in eel(Anguilla japonica),and several tissues of PYR were investigated after third oral administration at the same dose in eel.The plasma and several tissues were collected at different interals after administration of PYR.The PYR concentrations in plasma and tissues were determined by high performance liquid chromatograph(HPLC) with a limit of detection of 0.005μg/mL(g).Chromatography seperation was achieved on a Agilent TC2C18 PN 5189352902(4.6 mm×150mm) column using a mixature of acetnonitrile and water and acetic acid(15:85:0.25 v/v/v) as the mobile phase.Detection wavelength is 236nm and mobile speed is 1.0mL/min.PYR was extracted from tissues after the suitable quality of sodium sulfate anhydrous was firstly added to both plasma and the other tissues and then two times extractions were respectively performed by mixed solution of acetonitrile and trichlormethane(10:1 v/v) and acetonitrile and trichlormethane(5:5 v/v),the recover rate were both over 80%,the coefficients of variation were less than 3%and the lowest detective limitwas 0.005μg/mL(μg/g).The method is validated for the analysis of various tissues:plasma,muscle,liver and kidney.Their linearity are all good over the concentration range(0～5.0μg/mL) in plasma and the concentration ranges(0～2.0μg/g) in tissues.The mean recoveries,within-day and between-day precisions fell within the ranges specified.The pharmacokinetic profiles following oral administration were determined utilizing a classical linear two-compartment open model and the pharmacokinetic equation is C=4.3606e-0.0873t+4.9431e-0.0864t-9.3037e-0.1335t. The results indicated that the apparent volume of distribution(Vd/F),absorption half-life(t1/2ka),distribution half-life(t1/2α) and elimination half-life(t1/2β) were 15.38L/Kg,5.19h,7.94h,8.02h respectively,and the area under the curve(AUC) was 37.45μg·h/mL;Following third oral administration at the same dosage,PYR could be detected in muscle,liver and kidney 60 days after dosing.And there was no residue higher than 0.05μg/g 60 days after withdrawal of administration in tissues.The results showed that the depletion of PYR in eel is slow with a long residue time.It was calculated that the withdrawl period should not be less than 60 days after oral administration of PYR in eel.

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CLC: > Agricultural Sciences > Aquaculture, fisheries > Fisheries Protection > Fisheries pharmacology, pharmacology
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