Pharmacokinetics And Bioavailability Of Compound Diclofenac Soidium Injection In Pig

Compound Diclofenac Soidium Injection is a new compound preparation,which is made up of Diclofenac Soidium and Paracetamol.It is clinically used for the treatment of swine's traumatic or surgery pain,and as an auxiliary treatment of febrile illness.The pharmacokinetics characteristics and bioavailability of Compound Diclofenac Soidium Injection in pigs were studied in this paper,in order to provide experimental evidence for the rational use of drugs.1 Determination of Diclofenac in pigs plasma with HPLCIn order to establish a HPLC method for the determination of plasma concentrations of diclofenac in pigs,hexane-isopropanol solution(90:10,V/V)was used for extracting and purifying diclofenac of plasma.The plasma concentrations of Diclofenac were measured by HPLC UV-Detector.The chromatography was carried on a C18 column,the mobile phase was composed of methanol-15 g·L-1 acetic acid(80:20,V/V).the detection wavelength was set at 276 nm for Diclofenac,and analysis based on the external standard method.Under the condition of this test,the linear ranges for Diclofenac were 0.05 ?g·mL-1?20.0 ?g·mL-1(R2=1.0000),the lowest limit of quantitation was 0.05 ?g·mL-1,and the ingredients showed good relationships between the peak area and the concentration.The inter-day and intra-day RSD was less than 4%and 6%.The recovery was between 85%and 97%.The method which appointed the extraction and purification techniques could be used for the determination the Diclofenac levels of plasma in pigs.2 Determination of paracetamol in pigs plasma with HPLCIn order to establish a HPLC method for the determination of plasma concentration of paracetamol in pigs,Ethyl acetate was used for extracting and purifying paracetamol of plasma.The plasma concentrations of Diclofenac were measured by HPLC UV-Detector.The chromatography was carried on a C18 column,the mobile phase was composed of methanol-water(20:80,V/V),the flow rate was 1.0 mL·min-1,and the detection wavelength was set at 248 nm for paracetamol,and analysis based on the external standard method.Under the condition of this test,the linear ranges for paracetamol were 0.025 ?g·mL-1?20.0 ?g·mL-1(R2?0.9999),the lowest limit of quantitation was 0.025?g·mL-1,and the ingredients showed good relationships between the peak area and the concentration.The inter-day and intra-day RSD was less than 4%and 6%.The recovery was between 85%and 93%.The method which appointed the extraction and purification techniques could be used for the determination the Paracetamol levels of plasma in pigs.3 Pharmacokinetics and bioavailability of Compound Diclofenac Soidium Injection in pigThe pharmacokinetics of Compound Diclofenac Soidium Injection was investigated following single intravenous and intramuscular administration respectively at a dosage of 1 mg·kg-1 which is based on the content of diclofenac sodium by a two-period cross over design method in eight weaned pigs.washout period is one week.The concentrations of diclofenac and paracetamol in plasma were determined by high performance liquid chromatography(HPLC)with UV detector,respectively.Pharmacokinetic parameters were obtained by WinNonlin(?)5.2 pharmacokinetic analysis software.After single intravenous administration of Compound Diclofenac Soidium Injection,the main pharmacokinetic parameters of diclofenac were as follow:T1/2?(1.36±0.35)h,Tmax(0.08±0.00)h,Cmax(7.52±0.16)?g·mL-1,MRT(1.30±0.28)h,CLB(0.12±0.02)L·h-1·kg-1,Vd(0.24±0.03)L·kg-1,AUC(8.08±1.35)h·?g·mL-1.and the main pharmacokinetic parameters of paracetamol were as follow:T1/2?(1.71±0.33)h,Tmax(0.08±0.00)h,Cmax(7.70±0.91)?g·mL-1,MRT(1.62±0.24)h,CLB(0.54±0.14)L·h-1·kg-1,Vd(1.33±0.47)L·kg-1,AUC(11.35±2.40)h·?g·mL-1.After a single dose of intramuscular injection of Compound Diclofenac Soidium Injection,the main pharmacokinetic parameters of diclofenac were as follow:T1/2?(1.55±0.31)h,Tmax(0.50±0.13)h,Cmax(3.99±0.18)?g·mL-1,MRT(1.98±0.19)h,AUC(9.16±1.36)h·?g·mL-1,F 99.6%,and the main pharmacokinetic parameters of paracetamol were as follow:T1/2?(1.93±0.21)h,Tmax(0.63±0.13)h,Cmax(5.61±0.42)?g·mL-1,MRT(2.36±0.29)h,AUC(14.10±2.12)h·?g·mL-1,F 109.8%.The results showed that the pharmacokinetic characteristics of diclofenac in pigs manifested the rapid and complete absorption,poor distribution,rapid elimination and the high bioavailability by the intramuscular administration,while the pharmacokinetic characteristics of paracetamol in pigs manifested the rapid and complete absorption,wide distribution,rapid elimination and the high bioavailability by the intramuscular administration.Both diclofenac and paracetamol of Compound Diclofenac Soidium Injection have similar pharmacokinetic characteristics in vivo,which established a material foundation for a synergistic or additive effect.