Comparison of Diclofenac Diethylamine Permeation Across Horse Skin from Five Commercial Medical Human Formulations

The aim of this study was to compare the penetration of diclofenac through horse skin in vitro and its efficacy in vivo when applied from five, commercially available, human medical formulations containing 1.16% diclofenac diethylamine. The rate of transdermal penetration of diclofenac varied between formulations. Also, estimated steady-state flux (Jss) was significantly different from that reported for human and rat skin. All the tested formulations produced a very weak and short-lasting antiedematous effect.     

Preparation of silk sericin beads using LiCl/DMSO solvent and their potential as a drug carrier for oral administration

Silk sericin (SS) was fabricated into beads using LiCl/DMSO solution as a solvent. Up to 30 % (w/v) of SS could be dissolved within 3 hours, and the shape of solidified SS depends on the concentration of SS. Ethanol was the best coagulant among alcohols, making beads with suitable mechanical strength for further application. SS beads swell more at a pH above the isoelectric point (pl) than below the pl. The pH and the presence of an enzyme greatly affect the dissolution rate of SS beads. Whereas only 10 % of SS beads were dissolved at pH 2.2 in the presence of pepsin, more than 45 % of SS beads were dissolved at pH 7.4 in the presence of trypsin. The release of drug was suppressed in a stomach-like environment while promoted in an intestine-like environment.     

The disposition of diclofenac in camels after intravenous administration

The pharmacokinetics of diclofenac was studied in camels (Camelus dromedarus) (n=6) following intravenous (i.v.) administration of a dose of 2.5 mg kg(-1) body weight. The metabolism and urinary detection time were also studied. The results obtained (median and range) were as follows: the terminal elimination half-life (t(1/2beta)) was 2.35 (1.90-2.73)h, total body clearance (Cl(T)) was 0.17 (0.16-0.21)lh kg(-1). The volume of distribution at steady state (V(SS)) was 0.31 (0.21-0.39)l(-1)kg(-1), the volume of the central compartment of the two compartment pharmacokinetic model (V(C)) was 0.15 (0.11-0.17)l kg(-1). Five metabolites of diclofenac were tentatively identified in urine and were excreted mainly in conjugate form. The main metabolite was identified as hydroxy diclofenac. Both diclofenac and hydroxy diclofenac, appear to be the main elimination route for diclofenac when administered i.v. in camels. Diclofenac could be identified up to 4 days following i.v. administration in camels using a sensitive gas chromatography/mass spectrometry (GC/MS) method.     

Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep

The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.     

双氯芬酸钠残留检测的质谱条件选择

为优化双氯芬酸(DCF)残留检测过程中的质谱参数,提高其检测灵敏度。在电喷雾离子源负离子(ESI~-)和正离子(ESI~+)模式下,分别对DCF标准溶液进行母离子和子离子扫描,以优化定量检测的参数;比较ESI~-和ESI~+条件下,标准溶液和空白肝脏加标样品定量离子的响应。结果显示,在ESI~-模式下,DCF存在明显的源内裂解现象,而ESI~+模式下则未出现类似现象;因此导致质量浓度为2 ng/mL的DCF标准溶液在ESI~-条件下定量离子的峰面积远低于ESI~+;ESI~-条件下,空白肝脏加标样品(0.5 ng/g,LOQ)中几乎检测不到定量离子,而ESI~+条件下定量离子的响应则可满足检测要求。鉴于DCF在ESI~-条件下可发生源内裂解,建议在DCF的残留检测中采用ESI~+模式。