Oxyphenbutazone

To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age.

16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old).

Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at –80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant.

Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups.

The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.

Inflammation is the most essential part of bodys immune system and responsible for diseases manifestation in asthma, rheumatoid arthritis, allergy, aging, autoimmune diseases and etc.During of these conditions, many cytokines were regulated.The pro-inflammatory cytokines perform an essential function in development of an effective defense against disease infections and progression.Along with cytokines many enzymes play a critical role in regulation of inflammation.The enzymes such as 5-LOX, COX-1 and COX-2 are vital targets.Objective of study is to comprehensive screening of highly potential and precise phytoconstituents from ethnomedicinally important Cassia auriculata Linn which may have potential inhibitors for pro-inflammatory targets.Methanol extract of Cassia auriculata Linn leaf was subjected to HR-LCMS anal.The phytochem. signature was analyzed and 85 phytochems. are taken for the mol. docking studies with pro-inflammatory markers.After, through screening 10 compounds were showing good binding energy with hydrogen bond interaction with all three targets.Further, these compounds were subjected to ADME property prediction, wherein 6 compounds were showing the parameter values within acceptable range.Toxicity prediction reveals the 5 compounds are non-toxic.Insilico investigations revealed that 5 phytoconstituents namely Gallic acid; 2,6-Dihydroxybenzoic acid, Kaempferol; N-(3-Benzooxazol-2-yl-4- hydroxy-phenyl)-2-ptolyloxyacetamide; and Glycophymoline of Cassia auriculata Linn methanol leaf extract are potentially inhibiting the inflammatory enzymes.The study identified the precise phytoconstituents from Cassia auriculata Linn for anti-inflammatory activity.