Effect of oral co-administration of frozen-dried grapefruit juice on pharmacokinetics of tramadol in dogs

Summary Tramadol is a centrally acting analgesic drug extensively metabolized in animal species. Its clinical response is mainly due to the M1 metabolite, poorly produced in dogs. Grapefruit-juice can inhibit the metabolism of different drugs in animals and humans. The aim of the present study was to evaluate the pharmacokinetics of tramadol and its major metabolites after co-administration of tramadol and frozen-dried grapefruit-juice. A balanced cross-over study was used involving six male Beagle dogs. They were administered with tramadol alone (5 mg/kg) or with tramadol (5 mg/kg) plus frozen-dried grapefruit-juice (10 g). The plasma concentration vs time curves showed significant differences during the first 4 h following drug administration. Tmax was at 1.33 and 1.70 h following tramadol and tramadol plus frozen-dried grapefruit-juice treatment, respectively. Significant differences were also shown in Cmax (490 vs 270 ng/ml) and AUC (11,610 vs 5,890 h·h·ng/ml). Significant differences between the treatments were shown in all the M1 parameters reported. M2 and M5 did not show significant differences after both administrations. In conclusion, the frozen-dried grapefruit-juice was shown to affect the plasma concentrations of M1, despite them being well below those reported in humans

Tyrosol-Enriched Tomatoes by Diffusion across the Fruit Peel from a Chitosan Coating: A Proposal of Functional Food

Chitosan is receiving increasing attention from the food industry for being a biodegradable, non-toxic, antimicrobial biopolymer able to extend the shelf life of, and preserve the quality of, fresh food. However, few studies have investigated the ability of chitosan-based coatings to allow the diffusion of bioactive compounds into the food matrix to improve its nutraceutical quality. This research is aimed at testing whether a hydrophilic molecule (tyrosol) could diffuse from the chitosan-tyrosol coating and cross the tomato peel. To this end, in vitro permeation tests using excised tomato peel and an in vivo application of chitosan-tyrosol coating on tomato fruit, followed by tyrosol quantification in intact fruit, peel and flesh during a seven-day storage at room temperature, were performed. Both approaches demonstrated the ability of tyrosol to permeate across the fruit peel. Along with a decreased tyrosol content in the peel, its concentration within the flesh was increased, indicating an active transfer of tyrosol into this tissue. This finding, together with the maintenance of constant tyrosol levels during the seven-day storage period, is very promising for the use of chitosan formulations to produce functional tomato fruit

Application of An Improved HPLC-FL Method to Screen Serine Palmitoyl Transferase Inhibitors

In this work, we reported the application and validation of an improved high-performance liquid chromatography method coupled with a fluorimetric detector (HPLC-FL) to screen the activity of two heterocyclic derivatives reported as serine palmitoyl transferase (SPT) inhibitors. The analytical conditions were optimized in terms of the derivatization procedure, chromatographic condition, extraction procedure, and method validation according to EMEA guidelines. Once fully optimized, the method was applied to assess the SPT-inhibitory activity of the above-mentioned derivatives and of the reference inhibitor myriocin. The obtained results, expressed as a percentage of residual SPT activity, were compared to those obtained with the reference radio immune assay (RIA). The good correlation between the two types of assay demonstrated that the improved HPLC-FL method is suitable for a preliminary and rapid screening of potential SPT-inhibitors

PHARMACOKINETICS OF TRAMADOL AFTER EPIDURAL ADMINISTRATION IN HORSES

Tramadol is a centrally acting analgesic structurally related to codeine and morphine. The aim of the present study was to evaluate the pharmacokinetic of tramadol and its major metabolites after caudal epidural administration in the horse. Six gelding male adult horses were assigned to receive epidural administration of tramadol at 2 mg/kg. Plasma substances detection was achieved using a HPLC-FL method. Tramadol was detectable after 5 minutes up to 8 hours after epidural administration. Metabolites plasma concentrations were found under the limit of quantification of the method; however negligible amounts of M2 was detected from 30 min up to 1 hour in three subjects. In conclusion, this study shows that tramadol administered by caudal route in horses produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to provide analgesia. Further study of the drug's safety and efficacy for the treatment of pain in horses is warranted

PHARMACOKINETIC EVALUATION OF TRAMADOL AND ITS MAJOR METABOLITES AFTER SINGLE ORAL SUSTAINED TABLET ADMINISTRATION IN THE DOG: A PILOT STUDY

The study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol (M2) and N–O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100 mg tablet to dogs. Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog while M2 and M5 were quantified in all of the dogs. The median values of Cmax (maximum plasma concentration), Tmax (time to maximum plasma concentration) and T1/2 (half-life) for tramadol were 0.04 (0.17–0.02) lg mL1, 3 (4–2) and 1.88 (2.211–1.435) h, respectively. M5 showed median values of Cmax, Tmax and T1/2 of 0.1 (0.19–0.09) lg mL1, 2 (3–1) and 4.230 (6.583–1.847) h, respectively. M2 showed median values of Cmax, Tmax and T1/2 of 0.22 (0.330–0.080) lg mL1, 4 (7–3) and 4.487 (6.395–1.563) h, respectively. The findings suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in the dog