The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac serum concentration of 5.88 ± 0.934 mg/L was reached after 0.80 ± 0.35 h. The absorption half-life was 0.36 ± 0.25 h, and the area under the concentration vs. time curve (AUC0→∞) was 20.32 ± 4.521 mgh/L. A monoexponential concentration decline and small volume of distribution (Vd) of 0.29 ± 0.100 L/kg indicated a rapid, but not extensive distribution of diclofenac between central and peripheral compartment(s). Total clearance was 0.13 ± 0.034 L/h/kg, and elimination half-life was short (1.67 ± 0.743 h), as a result of a rapid distribution and extensive metabolism of diclofenac in the pig's body. When administered i.m. to pigs, diclofenac is absorbed and distributed rapidly. Distribution is not extensive, suggesting that diclofenac is predominantly retained in the central compartment. The elimination of the drug from the pig's circulation is also rapid, most of it probably being a result of extensive metabolism in the liver

Aims Generic products can be regarded as therapeutically equivalent and switchable with the reference product. However, switchability between generics is unknown, as direct comparisons between generics are not performed. The aim of this study was to investigate the bioequivalence between generic clopidogrel products by means of adjusted indirect comparisons (AICs). Methods AICs were conducted to assess bioequivalence between 4 generic clopidogrel products that are authorised in Serbia. Generics are considered equivalent to the reference if the 90% confidence intervals (CIs) for the ratios test/reference of the maximum concentration (Cmax) and area under the curve up to the last measurable concentration (AUC0–t) fall within the acceptance range 80.00–125.00%. However, for AICs between generics, the Canadian acceptance criterion for Cmax was employed, where only the point estimate of Cmax needs to be within 80.00–125.00%. Results The 90% CIs of the AICs demonstrated bioequivalence within 80.00–125.00% for all AUC0–t comparisons. The point estimates of Cmax in all AICs were also within this range. Conclusion This study demonstrates that the bioavailability of these 4 generic clopidogrel products authorised in Serbia is very similar. Despite the limited power of AICs, bioequivalence was demonstrated for all 90% CIs of AUC0–t and all 90% CIs of Cmax comparisons were within or very close to the acceptance range, being able to comply with the acceptance criterion employed in Canada for Cmax. Therefore, these 4 generic clopidogrel products authorised in Serbia can be considered switchable with each other in clinical practice based on the adjusted indirect comparisons.

Diclofenac residue (DF) in swine tissue (liver, kidney, muscle, injection site) were examined using the method of High Performance Liquid Chromatography (HPLC) 15h, 72h,and 120h after i.m. administration of an individual therapeutic dose of diclofenac-sodium. At 15h after administration, the highest concentration of DF was found in the kidney (0.614 mg/kg), while a concentration about two times lower was found in the liver (0.316 mg/kg). At the injection site, the DF concentration was 0.432 mg/kg, while DF remained in a very low concentration (0.052 mg/kg) in the muscle outside the injection site, which was the lowest concentration in comparison with all the other examined tissues. At 72h after administration, DF was present in all examined tissues, but its concentrations were lower than the level that could be determined using the analytic procedure. Traces of the administered medicine disappeared after the waiting period of 120h in all tissues, except for the injection site. The longer presence of the medicine at the injection site could be a consequence of local inflammation, or irritation, that could cause a reduction in pH values of the area around the injection site, thus leading to slower dissolving and a longer presence of the DF at the injection site