复方双氯芬酸钠注射液在猪体内药动学和生物利用度研究

[目的] 通过对复方双氯芬酸钠注射液在猪体内的药动学研究,了解其活性组分在猪体内的过程和生物利用度,为制定临床合理给药方案提供依据。[方法] 采用随机交叉试验设计,8头健康断奶仔猪分别单剂量静脉和肌内注射复方双氯芬酸钠注射液,注射剂量均为1 mg？kg-1(以双氯芬酸钠计),两阶段洗脱期为2周。采用经验证的高效液相色谱法分别测定血浆中双氯芬酸和对乙酰氨基酚的浓度,实测血药浓度-时间数据采用WinNonlin?5.2版药动学分析软件拟合药动学参数。[结果] 单剂量静脉注射复方双氯芬酸钠后,猪体内双氯芬酸主要药动学参数分别为:T1/2β=(1.36±0.35)h,Tmax=(0.08±0.00)h,Cmax=(7.52±0.16) μg？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？μg？mL-1;对乙酰氨基酚主要药动学参数分别为:T1/2β=(1.71±0.33)h,Tmax=(0.08±0.00)h,Cmax=(7.70±0.91) μg？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？μg？mL-1。猪单剂量肌内注射复方双氯芬酸钠注射液后,猪体内双氯芬酸主要药动学参数分别为:T1/2β=(1.55±0.31)h,Tmax=(0.50±0.13)h,Cmax=(3.99±0.18) μg？mL-1,MRT=(1.98±0.19)h,AUC=(9.16±1.36)h？μg？mL-1,F=113.6%;对乙酰氨基酚主要药动学参数分别为:T1/2β=(1.93±0.21)h,Tmax=(0.63±0.13)h,Cmax=(5.61±0.42) μg？mL-1,MRT=(2.36±0.29)h,AUC=(14.10±2.12)h？μg？mL-1,F绝对=124.3%。结果表明:双氯芬酸和对乙酰氨基酚在猪体内均能迅速消除,但双氯芬酸在猪体内分布较差,对乙酰氨基酚则广泛分布;肌内注射给药后,双氯芬酸和对乙酰氨基酚自注射部位吸收均迅速且完全。[结论] 复方双氯芬酸钠注射液无论静注还是肌内注射给药,两种活性成分在猪体内具有相似的药动学特征。
[Objectives] The pharmacokinetics characteristics and bioavailability of compound diclofenac sodium injection in pigs were studied in this paper, in order to provide experimental evidence for the rational use of drugs.[Methods] The pharmacokinetics of compound diclofenac sodium 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 piglets, washout period is two 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.[Results] After single intravenous administration of compound diclofenac sodium injection, the main pharmacokinetic parameters of diclofenac were as follows:T1/2β=(1.36±0.35)h, Tmax=(0.08±0.00)h, Cmax=(7.52±0.16) μg？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？μg？mL-1, and the main pharmacokinetic parameters of paracetamol were as follows:T1/2β=(1.71±0.33)h, Tmax=(0.08±0.00)h, Cmax=(7.70±0.91) μg？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？μg？mL-1. After a single dose of intramuscular injection of compound diclofenac sodium injection, the main pharmacokinetic parameters of diclofenac were as follows:T1/2β=(1.55±0.31)h, Tmax=(0.50±0.13)h, Cmax=(3.99±0.18) μg？mL-1, MRT=(1.98±0.19)h,