Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

Evaluation of a core collection of Brassica oleracea accessions for resistance to Brevicoryne brassicae, the cabbage aphid

A rapid, simple and reliable technique was developed for evaluating Brassica accessions in the glasshouse for resistance to Brevicoryne brassicae, the cabbage aphid. Brassica accessions were grouped into crop types with similar habit and vigour for evaluation. 401 Brassica oleracea accessions, representing the genetic and geographic diversity of the species, were evaluated for resistance to a population of B. brassicae collected originally from HRI, Wellesbourne. Ninety eight accessions were identified as being moderately resistant (grade 3) or partially resistant (grade 4). Re-testing of accessions in the glasshouse identified 12 moderately resistant and 43 partially resistant accessions. The most promising gene pool was kale, where a higher than expected number of resistant accessions were found. Three of the kales were consistently rated as moderately resistant in all tests. In contrast the broccoli gene pool was a poor source of resistance with less (one out of 46) resistant accessions than expected. Eleven of the kales graded 3 were tested in the field in 1995 and resistance to B. brassicae was confirmed. Ten accessions were also tested for resistance to two additional populations of B. brassicae, one from Greece and the other from Portugal. The results provided no evidence of aphid biotype/host specific differences in the resistance of these B. oleracea accessions. This revised version was published online in August 2006 with corrections to the Cover Date.