Comments on the method to test side effects of pesticides on the predatory mitePhytoseiulus persimilis Ath.-Hen

A paper published byKniehase & Zoebelein (1990) describes a new laboratory method to test the side effects of pesticides on the predatory mitePhytoseiulus persimilis and criticizes the laboratory test developed by the International Working Group pesticides and beneficial organisms of the International Organization for Biological Control (IOBC), West Palaearctic Regional Section (WPRS). The present publication discusses the advantages and disadvantages of both methods, responds to the criticism and mention the overall concept of the IOBC/WPRS Working Group including semifield and field test methods.In einer Arbeit vonKniehase undZoebelein (1990) wird ein neues Laborverfahren zur Prüfung der Nebenwirkung von Pflanzenschutzmitteln auf die RaubmilbePhytoseiulus persimilis beschrieben. Die genannten Autoren äußern sich kritisch über das seither von der Arbeitsgruppe Pflanzenschutzmittel und Nutzorganismen der International Organization for Biological Control (IOBC), West Palaearctic Regional Section (WPRS) praktizierte Verfahren. In der vorliegenden Arbeit werden die Vor- und Nachteile der beiden Prüfmethoden diskutiert. Einer Reaktion auf die Kritik folgt eine kurze Beschreibung der gesamten Konzeption der genannten Arbeitsgruppe, die auf einer Kombination aus Labor-, Halbfreiland- und Feldprüfverfahren beruht.     

Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles

The pharmacokinetics of a multidose regimen of potassium bromide (KBr) administration in normal dogs was examined. KBr was administered at 30 mg/kg p.o. q 12 h for a period of 115 days. Serum, urine, and cerebrospinal fluid (CSF) bromide (BR) concentrations were measured at the onset of dosing, during the accumulation phase, at steady-state, and after a subsequent dose adjustment. Median elimination half-life and steady-state serum concentration were 15.2 days and 245 mg/dL, respectively. Apparent total body clearance was 16.4 mL/day/kg and volume of distribution was 0.40 L/kg. The CSF:serum BR ratio at steady-state was 0.77. Dogs showed no neurologic deficits during maintenance dosing but significant latency shifts in waves I and V of the brainstem auditory evoked response were evident. Following a subsequent dose adjustment, serum BR concentrations of approximately 400 mg/dL were associated with caudal paresis in two dogs. Estimated half-life during the accumulation phase was shorter than elimination half-lives reported in other studies and was likely related to dietary chloride content. The range of steady-state concentrations achieved suggests individual differences in clearance and bioavailability between dogs. The described protocol reliably produced serum BR concentrations that are required by many epileptic patients for satisfactory seizure control.     

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous‐rate infusion in the horse

Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra‐operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration–effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic–pharmacodynamic (PK‐PD) actions of GLY during and after a 2‐h constant‐rate intravenous infusion (4 μg/kg/h) and evaluate potential PK‐PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri‐exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8‐h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment.     

The pharmacokinetics of glycopyrrolate in Standardbred horses

The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V₁), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC_0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.     

Bioavailability, disposition kinetics and dosage of sulfadimethoxine in dogs--a correction.

A reevaluation of the disposition kinetics and extent of absorption of sulfadimethoxine in normal dogs following intravenous and oral dosage has been made. The tissue to plasma level ratio at the peak tissue level (k12/k21) was 0.55, while the tissue to plasma level ratio after distribution equilibrium (k12/k21-beta) was 0.926. The systemic availability of sulfadimethoxine from the oral suspension was 48.8% (24.4-86.2) when corrections for intrasubject variability were made.     

In vitro comparison of three fixation methods for humeral fracture repair in adult horses

The stiffness, load to failure, and bending moments of adult intact equine humeri and humeri repaired with 3 fixation techniques were determined in vitro. Bones were tested in axial compression (30 pairs), mediolateral 3-point bending (15 pairs), and caudocranial 3-point bending (15 pairs). An oblique osteotomy of 1 humerus of each pair was performed to simulate the long spiral oblique fractures that occur clinically in horses. Bones were repaired in 3 ways: group 1--nylon band cerclage fixation (20 bones); group 2--multiple intramedullary pinning (20 bones); and group 3--nylon band cerclage fixation and multiple intramedullary pinning (20 bones). Intact bones were significantly (P less than 0.05) stronger than repaired bones in each testing mode. Bones repaired with bands only were significantly less stiff in bending than were bones repaired with pins only or with pins and bands. In compression, only specimens repaired with pins and bands were significantly stiffer than were bones repaired with bands only. Bones repaired with bands only required significantly less load to failure in compression and in caudocranial bending than did bones repaired with pins only or with pins and bands. Bones repaired with pins only deformed through the full displacement of the actuator (5 cm), and pins deformed plastically. Bones repaired with pins and bands were stiffer and had higher bending moments than did bones repaired with pins only, but the differences were not significant.     

Characterization of the pharmacokinetic and pharmacodynamic properties of the angiotensin-converting enzyme inhibitor, enalapril, in horses

The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin-angiotensin-aldosterone system, angiotensin I (0.5 microg/kg) was administered at fixed intervals, followed by blood-pressure and heart-rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after i.v. administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency (P = .0625) toward a decrease in ACE activity 45-120 minutes after enalapril administration, but ACE activity suppression was never > 16%. There was a tendency (P = .0625) toward a decrease in mean arterial pressure (MAP) 6-8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency (P = .0625) toward a decrease in the MAP response 4-24 hours after enalapril administration. Single-dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.     

Pharmacokinetic and pharmacodynamic evaluation of intravenous hydromorphone in cats

This study describes the pharmacokinetics of intravenous hydromorphone in cats and the simultaneous measurement of antinociceptive pharmacodynamic effects using a thermal threshold testing system. Following establishment of a baseline thermal threshold, six adult cats were administered 0.1 mg/kg of hydromorphone intravenously. Thermal threshold testing and blood collection were conducted simultaneously at predetermined time points. Plasma hydromorphone concentrations were determined by a liquid chromatographic-mass spectral method and pharmacokinetic analysis was performed by nonlinear least squares regression analysis. Plasma hydromorphone concentrations declined rapidly over time, and were below the limit of quantification of the assay (LOQ = 1.0 ng/mL) by 360 min. In contrast, thermal thresholds rose from a pretreatment value of 40.9 +/- 0.65 degrees C (mean +/- SEM) to instrument cut-out (55 degrees C) within 15 min and remained significantly elevated from 15-450 min after treatment. Inspection of the data revealed no direct correlation between plasma hydromorphone concentrations and the antinociceptive effect of this drug in cats. These findings support the importance of conducting pharmacokinetic studies in parallel with objective measurements of drug effect.