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1.
The evolution of strong organophosphorus multiresistance, suppressible by S,S,S-tributyl phosphorotrithioate (TBPT), in a California strain of Culex pipiens fatigans was examined by further selection with temephos, alone and in combination with the synergists TBPT or piperonyl butoxide (PB). Selection by temephos and temephos + PB increased resistance to higher levels. However, selection by temephos + TBPT virtually abolished TBPT-suppressible resistance while preventing the emergence of significant alternative resistance mechanisms. The phenomenon of synergism may enable the extended use of an insecticide where alternative resistance mechanisms are either absent or of low efficiency in the target population. 相似文献
2.
Bruno H. Pypendop Kristine T. Siao M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(3):269-277
Objective
To determine the effective plasma alfaxalone concentration for the production of immobility in cats.Study design
Prospective up-and-down study.Animals
Sixteen 1–2 year old male castrated research cats.Methods
Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered via the medial saphenous catheter, using a target-controlled infusion system. The infusion lasted for approximately 32 minutes. A noxious stimulus (tail clamp) was applied 30 minutes after starting the alfaxalone infusion, until the cat moved or 60 seconds had elapsed, whichever occurred first. The target alfaxalone concentration was set at 5 mg L?1 in the first cat and increased or decreased by 1 mg L?1 in subsequent cats, if the previous cat had moved or not moved in response to stimulation, respectively. This was continued until six independent crossovers (different responses in pairs of subsequent cats) had been observed. Blood samples were collected before alfaxalone administration, and 15 and 31 minutes after starting the administration, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. The alfaxalone concentration yielding a probability of immobility in 50% (EC50), 95% (EC95) and 99% (EC99) of the population, and their respective 95% Wald confidence intervals were calculated.Results
The EC50, EC95 and EC99 for alfaxalone-induced immobility were 3.7 (2.4–4.9), 6.2 (4.7–) and 7.6 (5.5–) mg L?1, respectively.Conclusions and clinical relevance
The effective plasma alfaxalone concentration for immobility in cats was determined. This value will help in the design of pharmacokinetic-based dosing regimens. 相似文献3.
Synthesis and evaluation of hydroxyazolopyrimidines as herbicides; the generation of amitrole in planta 下载免费PDF全文
4.
The bioequivalence of a single intravenous administration of the anesthetic alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives in cats 下载免费PDF全文
K. Pasloske M. G. Ranasinghe S. Sauer J. Hare 《Journal of veterinary pharmacology and therapeutics》2018,41(3):437-446
To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single‐dose, randomized, two‐period, two‐sequence, cross‐over bioequivalence study with a 7‐day washout period between treatments. Twenty‐four (12 neutered males and 12 intact females), healthy, adult cats weighing 4.1±0.9 kg. Cats were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using a randomized cross‐over design. One‐milliliter venous blood samples were collected at predetermined time points to 12 hr after drug administration to determine alfaxalone plasma concentration over time. Alfaxalone concentrations were determined by a validated analytical testing method using HPLC‐MS/MS. Plasma profiles of alfaxalone concentration against time were analyzed by noncompartmental analysis. The pivotal variables for bioequivalence were AUClast and Cmax. Equivalence was achieved if the 90% confidence interval for AUClast and Cmax fell into the asymmetric ±20% interval (0.80–1.25). Physiological variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX was used for nonnormally distributed data. VAS scores were analyzed as for blood bioequivalence data. Variables were evaluated for safety and assessed at alpha = 0.10. Cmax and AUClast for Reference and Test Products were statistically bioequivalent. No physiological variables except for a drug by time interaction for respiratory rate differed between treatment groups, and this difference was not clinically relevant. No anesthetic event times or VAS scores for quality of anesthesia were different between treatment groups. Neither formulation caused pain upon injection. The Reference and Test Products are pharmaceutically bioequivalent formulations when administered as a single intravenous administration for the purpose of induction of anesthesia in cats. 相似文献
5.
Bruno H. Pypendop M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(4):459-466
Objective
To compare the performance of an alfaxalone constant rate intravenous (IV) infusion versus a 3-step IV infusion, both following a loading dose, for the maintenance of a target plasma alfaxalone concentration of 7.6 mg L–1 (effective plasma alfaxalone concentration for immobility in 99% of the population) in cats.Study design
Prospective randomized crossover study.Animals
A group of six healthy, adult male neutered cats.Methods
Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for drug administration. An IV bolus of alfaxalone (2 mg kg–1) was administered, followed by either 0.2 mg kg?1 minute?1 for 240 minutes (single infusion; SI) or 0.4 mg kg?1 minute?1 for 10 minutes, then 0.3 mg kg?1 minute?1 for 30 minutes, and then 0.2 mg kg?1 minute?1 for 200 minutes (3-step infusion; 3-step). Plasma alfaxalone concentration was measured at six time points during the infusions. Measures of performance were calculated for each infusion regimen and compared using the paired Wilcoxon signed-rank test.Results
Median (range) absolute performance error, divergence, median prediction error and wobble were 15 (8–19)%, ?8 (?12 to ?6)% hour?1, ?12 (?19 to ?7)% and 10 (8–19)%, respectively, in the SI treatment, and 6 (2–16)%, 0 (?13 to 2)% hour?1, 1 (?16 to 4)% and 4 (3–6)% respectively, in the 3-step treatment and were significantly smaller in the 3-step treatment than in the SI treatment.Conclusion and clinical relevance
After IV administration of a bolus dose, a 3-step infusion regimen can better maintain stable plasma alfaxalone concentrations close to the target concentration than a single constant rate infusion. 相似文献6.
C. Lau M. G. Ranasinghe I. Shiels H. Keates K. Pasloske M. C. Bellingham 《Journal of veterinary pharmacology and therapeutics》2013,36(5):516-520
Alfaxalone (3α‐hydroxy‐5α‐pregnane‐11, 20‐dione) is a neuroactive steroid with anaesthetic properties and a wide margin of safety. The pharmacokinetic properties of alfaxalone administered intravenously and intraperitoneally in rats (n = 28) were investigated. Mean t1/2elim for 2 and 5 mg/kg i.v. was 16.2 and 17.6 min, respectively, but could not be estimated for IP dosing, due to sustained plasma levels for up to 60 min after injection. Clp for i.v. injection was calculated at 57.8 ± 23.6 and 54.3 ± 6.8 mL/min/kg, which were 24.5% and 23% of cardiac output, respectively. The observed Cmax was 3.0 mg/L for IP administration, and 2.2 ± 0.9 and 5.2 ± 1.3 mg/L for 2 and 5 mg/kg i.v. administration, respectively. AUC0–60 was 96.2 min·mg/L for IP dosing. The relative bioavailability for IP dosing was 26% and 28% compared to i.v. dosing. Differences in t1/2elim and Clp from previous pharmacokinetic studies in rats are likely due to variations in alfaxalone formulation rather than sex differences. Alfaxan® given IP caused sustained levels of alfaxalone, no apnoea and longer sleep times than i.v. dosing, although immobilization was not induced in 30% of rats given Alfaxan® IP. A pharmacodynamic study of the effects of combining IP injection of Alfaxan® with other premedication agents is worthwhile, to determine whether improved anaesthesia induction could ultimately provide an alternative anaesthetic regimen for rats. 相似文献
7.
Ferré PJ Pasloske K Whittem T Ranasinghe MG Li Q Lefebvre HP 《Veterinary anaesthesia and analgesia》2006,33(4):229-236
OBJECTIVE: To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU). EXPERIMENTAL DESIGN: Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood samples were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD. RESULTS: The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant; the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses. 相似文献
8.
Bruno H. Pypendop M.G. Ranasinghe Kirby Pasloske 《Veterinary anaesthesia and analgesia》2018,45(5):630-639
Objectives
To determine the context-sensitive half-time of alfaxalone following intravenous infusions of various durations. To estimate the time necessary for plasma concentration to decrease by up to 95%.Study design
Prospective randomized and simulation studies.Animals
A group of six 1-year-old male castrated research cats.Methods
Cats were instrumented with catheters in a jugular and a medial saphenous vein. Alfaxalone was administered using a target-controlled infusion system, to target a plasma alfaxalone concentration of 7.6 mg L–1. The infusion lasted 30 (n = 2), 60 (n = 2) or 240 (n = 2) minutes. Blood samples were collected prior to drug administration, and at several times during and up to 8 hours after the infusion, for the determination of plasma alfaxalone concentration using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to each time–concentration profile, and a population model was fitted to data from all individuals. The context-sensitive half-time was determined from each individual model. In addition, times for plasma alfaxalone concentration to decrease by 50–95% following bolus administration and target-controlled infusions or continuous rate infusions of 0.5–8 hours were estimated by simulation using the population model.Results
Context-sensitive half-times were 2 and 8, 6 and 9, and 18 and 20 minutes for the 30, 60 and 240 minutes, respectively. Time for plasma alfaxalone concentration to decrease by 90% was predicted to range from 7 to 120 or 113 minutes following a bolus to an 8 hour target-controlled or continuous rate infusion, respectively.Conclusion and clinical relevance
Recovery time from alfaxalone anesthesia in cats is predicted to be influenced by the duration of target-controlled infusion. 相似文献9.
Rahularaj R. Deshapriya R. M. C. Ranasinghe R. M. S. B. K. 《Tropical animal health and production》2019,51(8):2413-2419
Tropical Animal Health and Production - A study was carried out to identify prevalence and risk factors for bovine subclinical mastitis (SCM) in crossbred lactating cows within the Kurunagala... 相似文献
10.
Wendy A. Goodwin Kirby Pasloske Helen L. Keates Millaganamada Gedara Ranasinghe Solomon Woldeyohannes Nigel Perkins 《Veterinary anaesthesia and analgesia》2019,46(2):188-199