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.     

The persistence of foot-and-mouth disease virus on wool

SUMMARY Five Suffolk sheep, held in a high-security isolation room, were exposed for 2 hours to the aerosol of 3 mature pigs that had been infected with foot-and-mouth disease virus (FMDV), strain O₁-BFS. The fleeces of 3 of the sheep were contaminated with FMDV at 2 days post exposure (dpe), while at 5 dpe the fleeces of all 5 sheep were more extensively, and more heavily, contaminated. The persistence of FMDV on contaminated wool was examined in vitro using multiple 0.5 g samples of Merino wool that were each contaminated with one of 3 strains of FMDV in tissue-culture medium: O₁-BFS, O-Morocco (O-MOR 9/91) or an Asia 1 strain (TAI 1/90). Wool samples were held at either 4°C, 18°C or 37°C, and decay curves were established for each virus at each temperature. These curves predicted that O₁-BFS, O-MOR 9/91 and TAI 1/90 would fall below detect-able levels at 72, 70 and 48 days post contamination (pc), respectively, for wool stored at 4°C; at 11, 12 and 12 days pc, respectively, for wool stored at 18°C; and at 57, 68 and 33 hours pc, respectively, for wool stored at 37°C. For wool contaminated with O₁-BFS-infected sheep faeces, urine or blood, or with O₁-BFS-infected cattle saliva, decay curves predicted virus to persist for 5 to 11 days pc at 18°C. We demonstrated that the simulated scouring of FMDV-contaminated wool at 60° to 70°C would usually reduce virus to below detectable levels. The detergent component of the scouring process had little, if any, antiviral activity, and scouring at 20°C or 50°C had limited impact on FMDV titres . We recommend that either (1) simple storage of FMDV-contaminated wool for 4 weeks at temperatures of 18°C or higher, or (2) scouring of contaminated wool at 60° to 70°C would be sufficient to remove the threat of FMDV-contaminated wool being infectious to other animals .     

Determination of Venus Winds by Ground-Based Radio Tracking of the VEGA Balloons

A global array of 20 radio observatories was used to measure the three-dimensional position and velocity of the two meteorological balloons that were injected into the equatorial region of the Venus atmosphere near Venus midnight by the VEGA spacecraft on 11 and 15 June 1985. Initial analysis of only radial velocities indicates that each balloon was blown westward about 11,500 kilometers (8,000 kilometers on the night side) by zonal winds with a mean speed of about 70 meters per second. Excursions of the data from a model of constant zonal velocity were generally less than 3 meters per second; however, a much larger variation was evident near the end of the flight of the second balloon. Consistent systematic trends in the residuals for both balloons indicate the possibility of a solar-fixed atmospheric feature. Rapid variations in balloon velocity were often detected within a single transmission (330 seconds); however, they may represent not only atmospheric motions but also self-induced aerodynamic motions of the balloon.     

Thermal structure of the venus atmosphere in the middle cloud layer

Thermal structure measurements obtained by the two VEGA balloons show the Venus middle cloud layer to be generally adiabatic. Temperatures measured by the two balloons at locations roughly symmetric about the equator differed by about 6.5 kelvins at a given pressure. The VEGA-2 temperatures were about 2.5 kelvins cooler and those of VEGA-1 about 4 kelvins warmer than temperatures measured by the Pioneer Venus Large Probe at these levels. Data taken by the VEGA-2 lander as it passed through the middle cloud agreed with those of the VEGA-2 balloon. Study of individual frames of the balloon data suggests the presence of multiple discrete air masses that are internally adiabatic but lie on slightly different adiabats. These adiabats, for a given balloon, can differ in temperature by as much as 1 kelvin at a given pressure.     

Implications of the VEGA Balloon Results for Venus Atmospheric Dynamics

Both VEGA balloons encountered vertical winds with typical velocities of 1 to 2 meters per second. These values are consistent with those estimated from mixing length theory of thermal convection. However, small-scale temperature fluctuations for each balloon were sometimes larger than predicted. The approximate 6.5-kelvin difference in temperature consistently seen between VEGA-1 and VEGA-2 is probably due to synoptic or planetary-scale nonaxisymmetric disturbances that propagate westward with respect to the planet. There is also evidence from Doppler data for the existence of solar-fixed nonaxisymmetric motions that may be thermal tides. Surface topography may influence atmospheric motions experienced by the VEGA-2 balloon.     

Overview of VEGA Venus Balloon in Situ Meteorological Measurements

The VEGA balloons made in situ measurements of pressure, temperature, vertical wind velocity, ambient light, frequency of lightning, and cloud particle backscatter. Both balloons encountered highly variable atmospheric conditions, with periods of intense vertical winds occurring sporadically throughout their flights. Downward winds as large as 3.5 meters per second occasionally forced the balloons to descend as much as 2.5 kilometers below their equilibrium float altitudes. Large variations, in pressure, temperature, ambient light level, and cloud particle backscatter (VEGA-1 only) correlated well during these excursions, indicating that these properties were strong functions of altitude in those parts of the middle cloud layer sampled by the balloons.