Plasma and Ocular Prednisolone Disposition after Oral Treatment in Cats

Abstract

Objective. To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. Methods. Six cats were administered with a single oral dose of prednisolone (10 mg). Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. Results. Mean ± standard error (SE) of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL) was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC) was 553.3 ± 120.0 ng∗h/mL and 378.8 ± 64.9 ng∗h/mL, respectively. A high AUCaqueous humor/AUCplasma ratio was observed (0.68 ± 0.13). The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. Clinical Significance. The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.

Effects of prednisolone on 1,2‐O‐dilauryl‐rac‐glycero glutaric acid‐(60‐methylresorufin) ester‐lipase activity and pancreatic lipase immunoreactivity in healthy cats

“…Given the fact that oral prednisolone reaches maximum concentration after approximately 1 hour in cats and has a half-life time of elimination of 0.66 hour, 33,34 we cannot exclude that measuring lipase 4 to 6 hours after drug administration would have led to different results.…”

“…However, the duration of action of prednisolone is believed to be between 12 and 26 hours. 34 Still, we believe this aspect is of minor clinical relevance because there are always variable time differences between blood sampling and tablet administration in daily practice.…”

“…Lipase half‐life time is unknown in cats. Given the fact that oral prednisolone reaches maximum concentration after approximately 1 hour in cats and has a half‐life time of elimination of 0.66 hour, 33,34 we cannot exclude that measuring lipase 4 to 6 hours after drug administration would have led to different results. However, the duration of action of prednisolone is believed to be between 12 and 26 hours 34 .…”

Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

“…MIC90 of ciprofloxacin is reported to be 0.5 µg/mL (33). Therapeutic concentration of prednisolone required to inhibit inflammatory mediated processes in AH (humans) is reported to be 25 ng/mL (34). Drugs levels for optimal activity are reported in terms of solution concentrations, which reflects the therapeutic levels needed in AH and VH tissues.…”

Numerical Optimization of Prednisolone–Tacrolimus Loaded Ultraflexible Transethosomes for Transdermal Delivery Enhancement; Box–Behnken Design, Evaluation, Optimization, and Pharmacokinetic Study

“…Isocratic elution was performed using acetonitrile and water (36:64) as the mobile phase (1) with a flow rate of 1.2 mL/min and a total time of 12 min. The liquid chromatography instrument was interfaced with a computer software using Microsoft Windows 7 [58].…”