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

• DOI: 10.1371/journal.pone.0176443
• Publication Date: 2017-04-26T17:34:05Z
• Authors: Graeme M. Doodnaught; Beatriz P. Monteiro; Javier Benito; Daniel Edge; Francis Beaudry; Ludovic Pelligand; Paulo Steagall
• Keywords: Crossover study; Pharmacodynamics

Background The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception a high-concentration formulation buprenorphine (Simbadol™) in cats. Methods Six healthy cats (4.9 ± 0.7 kg) were included prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) administered by subcutaneous (SC; 0.24 kg-1), intravenous (IV; 0.12 kg-1) or buccal (OTM; route administration thresholds (TT) compared with saline group (SAL). Thermal threshold testing blood sampling performed at predetermined time points up 72 hours including placebo group. Plasma norbuprenorphine concentrations measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic simultaneously fitted data from two analytes/three routes administration. Temporal changes TT analyzed one-way ANOVA followed Dunnett's test treatment comparisons two-way Bonferroni's correction (P < 0.05). Results significantly increased after SC, IV OTM 1–24 (except 2 hours), 0.5–8 6 1–8 respectively, when baseline. SC (1–30 (1–8 hours) (1–12 SAL, but not different among buprenorphine-treated absolute clearance 0.98 L kg-1 hour-1, volume distribution steady state 7.9 elimination-half-life 12.3 hours. Bioavailability for 94% 24%, respectively. Subcutaneous absorption biphasic. An initial peak (0.08 slow (half-life 11.2 progressive (peak acceleration 2.8 uptake. Conclusion characterized prolonged half-life sustained plasma yielding long-lasting (≥ 24 routes.