13 research outputs found
Doxycycline pharmacokinetics in geese
Funding Information: This work was supported by University of Pisa (ex 60%). The authors acknowledge ThothPro (Gdansk, Poland) for supplying the software used for the pharmacokinetic analysis. The authors are grateful to Mr. Zbigniew Kołodziej (Majątek Rutka, Puchaczow, Poland) for assistance conducting animal experiment and for supplying animals and facilities. The authors sincerely thank Dr. Victoria Llewelyn (Flinders University, Australia) for the scientific and English editing of the manuscript. Funding Information: This work was supported by University of Pisa (ex 60%). The authors acknowledge ThothPro (Gdansk, Poland) for supplying the software used for the pharmacokinetic analysis. The authors are grateful to Mr. Zbigniew Ko?odziej (Maj?tek Rutka, Puchaczow, Poland) for assistance conducting animal experiment and for supplying animals and facilities. The authors sincerely thank Dr. Victoria Llewelyn (Flinders University, Australia) for the scientific and English editing of the manuscript. Publisher Copyright: © 2021 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley &Sons Ltd.The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations have been performed to investigate the predicted plasma concentration after either a 10 or 20 mg/kg daily administration repeated consecutively for 5 days. Ten geese were enrolled in a two-phase cross-over study with a washout period of two weeks. All animals were treated intravenously and orally with doxycycline, and blood samples were collected up to 48 h after drug administration. Sample analysis was performed using a validated HPLC-UV method. A non-compartmental approach was used to evaluate the pharmacokinetic parameters of the drug. A long elimination half-life was observed (13 h). The area under the curve was statistically different between the two treatments, with the oral bioavailability being moderate (43%). The pharmacokinetic/pharmacodynamic index (%T>MIC) during the 48 h treatment period in the present study (71%) suggests that doxycycline appears to have therapeutic efficacy against some Mycoplasma species in the goose. The multiple-dose simulations showed a low accumulation index. A dosage of 10 mg/kg/day for 5 days seemed to be adequate for a good therapeutic efficacy without reaching unnecessarily high plasma concentrations.publishersversionPeer reviewe
Effect of feeding on the pharmacokinetics of vilazodone in dogs
Vilazodone (VLZ) is a drug approved for the treatment of major depressive disorder in humans but no data are available for dogs. The present study aimed to evaluate the pharmacokinetics of a single oral 40 mg dose of VLZ in healthy Labrador dogs (n = 6) in fasted and fed conditions. Dogs were randomly divided in two (n = 3) groups in a cross-over study design (2 x 2). Group I was administered with VLZ at 40 mg/dog after fasting over-night. Group II was fed prior to and after administration of the same dose. A two-week wash-out period was observed. Plasma samples collected underwent LC-MS/MS analysis. VLZ concentrations were quantified in dogs' plasma in two different windows of time: 30 min to 10 h for the fasted group and 4 h to 35 h for the fed group. The values for t(1/2 lambda z) were statistically different between the groups (fed, 4.6 +/- 1.1 h vs fasted, 1.7 +/- 0.2 h). Tmax drastically changed between the groups (fed, 10 h vs fasted, 1.5 h), while C-max did not significantly vary (fed, 39.4 +/- 5.6 ng/mL vs fasted, 38.7 +/- 4.8 ng/mL). The AUC value was always statistically higher in the fed group. As a result, the average relative oral fasted bioavailability of VLZ was low, 28.8 +/- 6.1%. In conclusion, feeding can affect the pharmacokinetics of VLZ in the dog
Effects of extreme temperatures on cardiovascular emergency hospitalizations in a Mediterranean region: a self-controlled case series study
Sintesi di analoghi del Sobetirome per il trattamento della sclerosi multipla
La sclerosi multipla (MS) è la principale malattia neurodegenerativa, di natura autoimmune, che colpisce il sistema nervoso centrale (SNC). Il complesso processo patologico alla base della malattia colpisce la mielina, sostanza multilamellare compreso nella guaina che avvolge gli assoni dei nervi, portando alla formazione di placche demielinizzate. Negli ultimi anni sono state compiute numerose ricerche nella speranza di sviluppare terapie riparative che hanno come scopo principale il ripristino di tale guaina attraverso l’azione sugli OPCs. Questi precursori sono capaci di proliferare e differenziarsi in oligodendrociti maturi (OLs) mielinizzanti. Sembra che gli ormoni tiroidei (THs) possano promuovere questo processo maturativo. Il lavoro svolto in questa tesi di laurea è stato indirizzato verso la sintesi di molecole TRβ-selettive al fine di limitare la gravità degli effetti collaterali provocati dall’attivazione non specifica dei TRs
Analytical Method Validation of Vilazodone with Spectrofluorimetric Detection in Rabbit Plasma
Vilazodone (VLZ) is an antidepressant agent approved in 2011 by Food and Drug Administration (FDA) for the treatment of major depressive syndromes. Its chemical structure derives from trazodone which is used as an off-label drug for dogs and cats in order to induce sedation and reduce anxiety, behavioural and pre-and post-operative stress. VLZ could be a potentially useful compound in reducing severe anxiety responses in pet animals. The aim of the present research was to develop and validate a method to quantify VLZ in rabbit plasma. A 500 μL aliquot of rabbit control plasma was added to 50 μL of IS (0.1 ug/mL) and 100 μL of NaOH 0.1M. Then 1 mL of Et2O:EtOAc (70:30 v/v) was added and the sample, shaken and centrifuged. The organic layer was transferred into a clean polypropylene vial. This procedure was repeated twice. The combined supernatants were evaporated under nitrogen at 40°C and reconstituted with 100 μL of mobile phase. 50 μL of this latter solution was injected onto HPLC-FL. The mobile phase consisted of Na 2 HPO 4 (0.02M, pH 5):ACN (67:33 v/v) at a flow rate of 1 mL/min. The analytical column (C18) was maintained at 40°C. Excitation and emission wavelengths were set at 353 and 486 nm, respectively. Times of retention of VLZ and IS were 3.26±0.09 and 4.70±0.08 minutes, respectively. The recovery of VLZ was about 83%. Limits of quantification and detection were 0.005 μg/mL and 0.001 μg/mL, respectively. This method was verified by determining VLZ concentration in rabbit plasma after a 1 mg/kg single IV administration. The analysis of samples allowed the calculation of the main pharmacokinetic parameters. In conclusion, the present research was able to quantify VLZ in rabbit plasma after VLZ administration. This method might have application for pharmacokinetic or toxicological studies
Pharmacokinetic profiles of meloxicam after single IV and PO administration in Bilgorajska geese
The purpose of this study was two-fold: I) to determine the pharmacokinetic profile of meloxicam (MLX) in geese after intravenous (IV) and oral (PO) administration and II) to assess tissue residues in muscle, heart, liver, lung, and kidney. Ten clinically normal female Bilgorajska geese were divided into two groups (treated, n = 8; control, n = 2). Group 1 underwent a 3-phase parallel study with a 1-week washout period. In phase I, animals received MLX (0.5 mg/kg) by IV administration; the blood was collected up to 48 hr. In phases II and III geese were treated orally at the same dosage for the collection of blood and tissue samples, respectively. Group 2 served as control. After the extraction procedure, a validated HPLC method with UV detection was used for plasma and organ analysis. The plasma concentrations were quantifiable up to 24 hr after both the administrations. The elimination phase of MLX from plasma was similar in both the administration groups. The clearance was slow (0.00975 L/hr*Kg), the volume of distribution small (0.0487 L/kg), and the IV half-life was 5.06 +/- 2.32 hr. The average absolute PO bioavailability was 64.2 +/- 24.0%. Residues of MLX were lower than the LOQ (0.1 mu g/kg) in any tested tissue and at any collection time. The dosage used in this study achieved the plasma concentration, which provides analgesia in Hispaniolan Amazon parrots for 5 out of 24 hr after PO administration. MLX tissue concentrations were below the LOD of the assay in tissue (0.03 mu g/ml). A more sensitive technique might be necessary to determine likely residue concentrations in tissue
Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues
Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites—glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites—paracetamol sulfate (PS) and p-Acetamidophenyl β-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard—4-Acetamidophenyl β-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese