A pharmacokinetic study of diclofenac sodium in rats

Abstract

The aim of the present study was to examine the pharmacokinetics of a single intravenous injection (i.v.) and oral administration (p.o.) of diclofenac sodium (DIC) in Sprague-Dawley (SD) rats. Twelve male SD rats were divided into 2 groups (n=6 per group); one group was injected intravenously with 2 mg/kg DIC, whereas the other group was lavaged with 2 mg/kg DIC. Blood samples were collected prior to DIC delivery (0 h) and 0.033, 0.083, 0.167, 0.25, 0.5, 1, 2, 4, 6, and 8 h post-administration. Blood plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) following pretreatment to induce protein precipitation. Pharmacokinetics software was applied to calculate relevant pharmacokinetic parameters using a non-compartmental model. Following i.v. administration of DIC, the terminal elimination rate constant (λ), apparent terminal elimination half-life (t), area under the concentration-time curve from time 0 extrapolated to infinity (AUC0), clearance (CL), apparent volume of distribution (V), mean residence time (MRT), and apparent volume of distribution at steady state (V) were 0.57±0.05 l/h, 1.22±0.11 h, 3356±238 h × ng/ml, 0.60±0.04 l/h, 1.05±0.10 l, 1.05±0.07 h and 0.63±0.07 l, respectively. Following p.o. administration of DIC, the λ, t, C, t, AUC, CL, V, MRT were: 0.63±0.12 l/h, 1.12±0.18 h, 1272±112 ng/ml, 0.19±0.04 h, 2501±303 h × ng/ml, 0.81±0.10 l/h, 1.29±0.12 l, and 2.70±0.18 h, respectively. The pharmacokinetic parameters of i.v. and p.o. DIC in rats show that the drug is rapidly absorbed, distributed, and eliminated.

Modulation of the In Vivo Inflammatory Response by Pro- Versus Anti-Inflammatory Intervertebral Disc Treatments

“…Polymers' and NC's preparation are described elsewhere [51,52], NCs characterization can be found in Appendix A ( Figure A1A) and NCs concentration used was 35 mg/mL (approximately 1.75 mg/kg). Df sodium salt (Sigma-Aldrich, St. Louis, MO, EUA) concentration used was 3 mg/mL (approximately 0.15 mg/kg), estimated based on the doses used in previous work in bovine IVD [16,18], intravenous (2 mg/kg) [53] or intraperitoneal (10 mg/kg) injections [25].…”

Penetration and pharmacokinetics of non‐steroidal anti‐inflammatory drugs in rat prostate tissue

“…After celecoxib, naproxen showed higher AUC and the other two NSAIDs ibuprofen and diclofenac had significantly lower AUCs in comparison to celecoxib and naproxen and therefore may not be good candidates for the treatment of CP/CPPS. The prostate tissue penetration ratios (AUC prostate /AUC plasma ) of NSAIDs were also calculated using reported plasma AUC's of NSAIDs from the literature . As expected, celecoxib showed the highest prostate tissue penetration ratio of 0.04 followed by naproxen‐0.031, ibuprofen‐0.0097, and diclofenac‐0.0092.…”

Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo

“…The hepatic phase I metabolism of diclofenac is mediated by human CYP2C9 and rat CYP2C11 [ 30 ]. The oral doses of phenacetin (20 mg/kg) and diclofenac (6 mg/kg) were selected based on previous rat pharmacokinetic studies [ 24 , 27 , 31 ]. Notably, the systemic exposure (AUC and C max ) of phenacetin was markedly enhanced by the concurrent administration of either intravenous honokiol or magnolol ( Figure 3 and Table 1 ), while that of diclofenac was not altered by the same treatment ( Figure 4 and Table 2 ).…”