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Modelo farmacocinético y farmacodinámico después de la administración subcutánea, intravenosa y bucal de una formulación de alta concentración de bupr

Descripción: La administración SC de Simbadol ™ se caracterizó por una vida media de absorción prolongada y concentraciones plasmáticas sostenidas que produjeron una antinocicepción de larga duración (≥ 24 horas) en comparación con las rutas IV y OTM

TITULO FUENTE ORIGINAL:

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

AUTORES:

Graeme M Doodnaught, Beatriz P Monteiro, Javier Benito, Daniel Edge, Francis Beaudry, Ludovic Pelligand, Paulo Steagall

REVISTA ABREV.:

PLoS One

AÑO:

2017

REFERENCIA:

12(4):e0176443

DOI:

10.1371/journal.pone.0176443

RESUMEN ORIGINAL:

Background: The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. Methods: Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the... + Leer más

Background: The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats.

Methods: Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett's test and treatment comparisons using two-way ANOVA with Bonferroni's correction (P < 0.05).

Results: Thermal thresholds were significantly increased after SC, IV and OTM from 1-24 hours (except 2 hours), 0.5-8 hours (except 6 hours), and 1-8 hours (except 6 hours), respectively, when compared with baseline. Thermal thresholds were significantly increased after SC (1-30 hours), IV (1-8 hours) and OTM (1-12 hours) when compared with SAL, but not different among buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake.

Conclusion: The SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes

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Enlace al pdf de acceso libre: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC[...]