Pharmacokinetics and pharmacodynamics of single and multiple-dose levamisole in belugas (Huso huso): Main focus on immunity responses.

The pharmacokinetics of levamisole were determined in the belugas after single intravascular (IV), and single and multiple-dose oral by feed administrations. Also, the effect of levamisole (LVM) on the stress and immune responses of belugas were assessed. One hundred-fourteen healthy belugas in 4 different groups received single LVM administration at the doses of 50 and 100 mg/kg via IV and oral routes. A separate group of 24 belugas were administered oral LVM at the dose of 100 mg/kg for 5 days. Blood samples were collected at different time points after administrations to measure plasma concentrations of LVM by a validated high-performance liquid chromatography (HPLC) assay. For immunological evaluations, a total of 126 belugas received 50 and 100 mg/kg LVM via medicated feed for 5 days or served as the control without any medication; blood samples were recovered on day 0, 1, 3, 5, 7, 10, and 14 to measure hemolytic activity of the complement system (HAC50), serum lysozyme activity, serum antibacterial activity, glucose, cortisol, total protein, albumin and C3 contents. In the single-dose administration, quantified LVM concentrations were dose-dependent and the oral bioavailability was in the range of 43.2-49.6%. In the multiple-dose administration, the peak plasma concentration at the steady state was 45.2 mg/ml, and accumulation ratio was calculated as 3.6. In the immunological study, LVM especially at the dose of 100 mg/kg increased HAC50, lysozyme and antibacterial activity in the sera of treated fish. No significant effect of LVM on glucose and albumin content was observed, but cortisol levels decreased and C3 content was increased, more significantly by LVM at the dose of 100 mg/kg. Our results indicate that LVM is well absorbed after oral administration and reached to concentrations that can affect stress indicators and improve immune responses in belugas.

Development and Validation of a Highly Sensitive Liquid Chromatography-Tandem Mass Spectrometry Technique to Determine Levamisole in Plasma and Saliva.

BACKGROUND: Levamisole is used as a steroid-sparing drug for the treatment of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome in children. As part of a large multicentre randomized controlled trial with levamisole, pharmacokinetic and pharmacodynamic parameters of levamisole in children with idiopathic nephrotic syndrome were investigated, as well as the feasibility of using saliva as an alternative and patient-friendly matrix for determining levamisole concentrations. In this study, the authors presented the development and validation of a highly sensitive method for determining levamisole in plasma and saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: In 100 µL samples, proteins were precipitated with 750 µL acetonitrile/methanol 420:80 (v/v) with levamisole-D5 as an internal standard. Calibration standards were prepared over a range of 0.1 ng/mL-50 ng/mL. To determine ultrafiltration efficiency, the ultrafiltrate was obtained by centrifuging blank plasma samples over the filter. Both filtered and nonfiltered samples were analyzed. RESULTS: For plasma, accuracy and within-run and between-run imprecision were between 95.0% and 100% and <14.5%, respectively, and for saliva, between 100.9% and 107.5%, and <13.3%. No significant matrix effects were observed. Samples were stable at benchtop for 24 hours and -80°C, for at least 14 months (stability experiments ongoing). The ultrafiltration efficiency of unbound concentrations in plasma was lower than 85% (58.9%) but stable, and, therefore, the observed concentration should be corrected. CONCLUSIONS: Based on observations, the developed measure can determine levamisole concentrations in participant saliva samples.

Pharmacokinetics of levamisole in the red-eared slider turtles (Trachemys scripta elegans).

The pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr-1  kg-1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 µg/ml, respectively, with 0.5 hr of Tmax . The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t1/2ʎz , can be recommended as an effective way for treating nematodes in turtles.

Plasma and Urine Levamisole in Clinical Samples Containing Benzoylecgonine: Absence of Aminorex.

Aminorex has been reported as a metabolite of levamisole in man, but data on the aminorex concentrations in clinical samples are scant. We thus measured levamisole, aminorex and benzoylecgonine in urine, and levamisole and aminorex in plasma using achiral liquid chromatography-high resolution mass spectrometry. Centrifuged urine (50 µL) was diluted with LC eluent containing internal standard (benzoylecgonine-D3, 25 µg/L) (450 µL). For plasma, sample (200 µL) and Tris solution (2 mol/L, pH 10.6, 100 µL) were added to a 60.5 × 7.5 mm i.d. glass test tube. Internal standard solution (ketamine-D4, 200 µg/L) (10 µL) was added and the tube contents vortex-mixed (5 s). Butyl acetate:butanol (9 + 1, v/v; 200 µL) was added and after vortex-mixing (30 s) and centrifugation (13,680 × g, 4 min), the extract was evaporated to dryness and reconstituted in 10 mmol/L aqueous ammonium formate containing 0.1% (v/v) formic acid (150 µL). Prepared samples and extracts (100 µL) were analyzed using an AccucoreTM Phenyl-Hexyl column (2.6 mm a.p.s., 100 × 2.1 mm i.d.) maintained at 40°C. MS detection was in positive mode using heated electrospray ionization (ThermoFisher Q-ExactiveTM). Intra- and inter-assay accuracy and precision were ±20%, and ≤11%, respectively, for all analytes in both matrices. Lower limits of quantitation were 0.1 and 1 µg/L (all analytes) in plasma and urine, respectively. Of 100 consecutive urine samples submitted for drugs of abuse screening containing benzoylecgonine, levamisole was detected in 72 (median 565, range 4-72,970 µg/L). Levamisole was also measured in eight plasma samples (median 10.6, range 0.9-64.1 µg/L). A number of metabolites of levamisole (4-hydroxylevamisole, levamisole sulfoxide, levamisole glucuronide, and hydroxylevamisole glucuronide) were tentatively identified in urine. Neither aminorex, nor any of its reported metabolites were detected in any sample.

Pharmaco-parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle.

The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and co-administered to calves naturally infected with susceptible gastrointestinal nematodes. The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control. RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance.

Monitoring of Levamisole Concentration in Serum of Traffic Participants after Cocaine Consumption.

This study highlights the problem of levamisole-adulterated cocaine in context of active traffic participation. For the purposes of levamisole concentration monitoring in human serum, an analytical method based on LC-MS/MS and solid-phase extraction was applied. A Luna 5 µm C18 (2) 100 A, 150 mm × 2 mm column and a mobile phase consisting of A (H2 O/methanol = 95/5, v/v) and B (H2 O/methanol = 3/97, v/v), both with 10 mM ammonium acetate and with 0.1% acetic acid (pH = 3.2), were used. The validation experiments demonstrated that the method applied was appropriate for levamisole quantification in human serum. For 23% of levamisole-positive samples, the concentrations exceeded 20 ng/mL. Therefore, the interaction of this drug with cocaine has to be considered as important for active traffic participation. As a consequence, monitoring of levamisole concentration in human serum is recommended, as long as it is used as cocaine adulterant.

Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome.

AIM: The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. METHODS: Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) levamisole (or placebo) orally once every other day. One hundred and thirty-six plasma samples were collected from 38 children from India and Europe and included in the analysis. A one compartment model described the data well. RESULTS: The apparent clearance rate (CL/F) and distribution volume (V/F) were 44 l h(-1) 70 kg(-1) and 236 l 70 kg(-1) , respectively; estimated interindividual variability was 32-42%. In addition to allometric scaling of CL/F and V/F to body weight, we identified a significant proportional effect of age on CL/F (-10.1% per year). The pharmacokinetics parameters were not affected by gender, tablet strength or study centre. The median (interquartile range) maximum plasma concentration of levamisole was 438.3 (316.5-621.8) ng ml(-1) , and the median area under the concentration-time curve was 2847 (2267-3761) ng ml(-1) h. Median tmax and t½ values were 1.65 (1.32-2.0) h and 2.60 (2.06-3.65) h, respectively. CONCLUSIONS: Here, we present the first pharmacokinetic data regarding levamisole in children with steroid-sensitive nephrotic syndrome. The pharmacokinetic profile of levamisole in children was similar to findings reported in adults, although the elimination rate was slightly higher in children.

Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration.

Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per os administration. Goats (n = 8) and sheep (n = 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t1/2λz) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.

Étant donné qu'il n'y a aucun anthelminthique homologué disponible pour utilisation chez les chèvres, l'utilisation hors-homologation de médicaments est une pratique usuelle dans la plupart des pays. L'objectif de la présente étude était de comparer la disposition pharmacocinétique de la combinaison levamisole (LVM)-oxyclozanide (OXZ) chez les moutons et les chèvres suite à l'administration per os. Des chèvres (n = 8) et des moutons (n = 8) âgés de 12 à 16 mois furent utilisés pour cette étude. Les animaux ont reçu une combinaison de comprimés de LVM et d'OXZ à une dose de 7,5 mg/kg et 15 mg/kg de poids corporel, respectivement. Des échantillons sanguins furent prélevés par ponction de la veine jugulaire à différents temps entre 5 min et 120 h suite à l'administration des médicaments. Les concentrations plasmatiques de LVM et d'OXZ furent analysées par HPLC suite à des procédures d'extraction de phase liquide-liquide. Les concentrations plasmatiques et les disponibilités systémiques de LVM et OXZ chez les chèvres étaient plus basses et la persistance plasmatique de LVM de plus courte durée comparativement à celles observées chez les moutons. Les demi-vies terminales (t1/2λz) des deux molécules sont plus courtes chez les chèvres comparativement à celles chez les moutons. Le traitement de chèvres avec la combinaison LVM-OXZ au dosage recommandé pour les moutons pourrait résulter en une efficacité moindre, dû à un sous-dosage, ce qui pourrait augmenter le risque de résistance au médicament chez les parasites. Des doses augmentées ou répétées pourraient s'avérer une stratégie pour obtenir des concentrations plasmatiques plus élevées et ainsi améliorer l'efficacité contre les parasites ciblés chez les chèvres comparativement aux moutons. Toutefois, quelques réactions indésirables peuvent survenir étant donné que le LVM a déjà un index thérapeutique assez étroit associé à sa structure et son effet apparentés à la nicotine.(Traduit par Docteur Serge Messier).

Evaluation of pharmacological interactions after administration of a levamisole, albendazole and ivermectin triple combination in lambs.

The goals of the current trial were (a) to characterize the plasma disposition kinetics of levamisole (LEV), albendazole (ABZ) and ivermectin (IVM), each administered either alone (single active ingredient) or as a combined formulation to lambs; (b) to compare the clinical anthelmintic efficacy of the same drugs given either separately or co-administered to lambs infected with resistant nematodes. Fifty Corriedale lambs naturally infected with multiple resistant gastrointestinal nematodes were involved in the following experimental trials: (a) "Pharmacokinetic trial": the animals were allocated into five groups (n=10 each) and intraruminally treated with either LEV (8 mg/kg), ABZ (5mg/kg), IVM (0.2mg/kg), or with a LEV+ABZ+IVM combined formulation, where each active ingredient was administered at the same dose. Blood samples were collected over 15 days post-treatment and drug plasma concentrations measured by HPLC. (b) "Efficacy trial": the same treated groups plus an untreated control group were used to assess the comparative anthelmintic efficacy by the faecal egg count reduction test (FECRT). Although the overall LEV disposition kinetics was unaffected, significantly lower (61%) ABZ-sulphoxide and higher (71%) IVM systemic availabilities were obtained after administration of the combined formulation in comparison to those obtained after treatment with each drug alone. A multiple drug resistance situation was observed for Haemonchus spp. The observed efficacies were 52% (LEV), 72% (ABZ), 80% (IVM) and 87% (triple combined formulation). The results reported here contribute to the pharmaco-therapeutic knowledge on drug combinations. This type of research is crucial before further development of combined anthelmintic preparations reaches the market to deal with resistant nematode control. The co-administration of LEV+ABZ+IVM did not result in a significant advantageous anthelmintic effect compared to the treatment with IVM alone. The simultaneous/combined administration of LEV, ABZ and IVM may account for a drug-drug pharmacological interaction in infected lambs. The pharmacokinetic interaction accounted for a reduced ABZ-sulphoxide and enhanced IVM systemic exposure following the combined treatment.

A sensitive method for the determination of levamisole in serum by electrochemiluminescence.

A novel method was developed for the determination of levamisole by electrochemiluminescence. The method was based on electrochemiluminescence signal enhancement produced by Ru(bpy)(3)(2+), which reacted with the tertiary amine group of levamisole on a platinum electrode in 12 mmol/L borate buffer (pH 9). A linear relationship between the luminous intensity and concentration of levamisole in the range 0-1 × 10(-7) mol/L was obtained and the detection limit was 1.76 × 10(-11) mol/L. The method is sensitive, selective, simple and convenient. The method has been successfully applied to the analysis of levamisole in serum.

Determination of levamisole in the plasma of patients with falciparum malaria using high-performance liquid chromatography.

BACKGROUND: The oral antihelmintic drug levamisole reduces sequestration of late stage parasites in falciparum malaria. Levamisole has been also identified as a cocaine adulterant. In the present study, authors developed a sensitive and selective HPLC-assay for the determination of levamisole in the plasma from patients with falciparum malaria. METHODS: Chromatographic separation was achieved by using a C18 column and with an isocratic elution system comprising phosphate buffer and acetonitrile. The eluate was monitored at 235 nm by diode array detection. RESULTS: The calibration curve for levamisole was linear in the range from 50 to 2000 ng/mL (r2 > 0.999). The limit of quantification was 28 ng/mL and the inter- and intraday coefficients of variation were less than 7%. No interference from commonly prescribed malaria treatments was observed. CONCLUSIONS: The HPLC method is simple, rapid, and robust and is suited for monitoring levamisole patients in routine or toxicological studies.

Bioanalytical methods for quantitation of levamisole, a widespread cocaine adulterant.

Abstract Levamisole is an anthelminthic that was first used as a de-worming agent in humans and animals. It has also been used to treat inflammatory conditions as well as certain types of cancer. Levamisole was discontinued for human use in the early 21st century due to toxic side effects including agranulocytosis and vasculitis. Recently, levamisole was discovered as a cocaine adulterant after reports emerged of drug users with the above disorders. As the prevalence of cocaine usage has grown in the last 15 years, measurement of levamisole in human samples has become increasingly important. This review focuses on the various bioanalytical methods available for the determination of levamisole in human plasma and urine. Earlier methods employed gas chromatography coupled with nitrogen-selective thermionic specific detection and nitrogen-phosphorus detection, as well as high performance liquid chromatography coupled with ultraviolet detection. In addition, gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) have also been described. Currently, GC-MS appears to be the method of choice however recent developments in the area of LC-MS/MS make this technology an attractive alternative. The merits of both GC-MS and LC-MS/MS for the determination of levamisole are evaluated on the basis of sample preparation, chromatographic separation conditions, run time, and analytical performance. In addition, emerging methods in this area are also reviewed.

Electromembrane extraction of levamisole from human biological fluids.

Electromembrane extraction coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for the determination of levamisole in some human biological fluids. Levamisole migrated from 4 mL of different acidized biological matrices, through a thin layer of 2-nitrophenyl octyl ether containing 5% tris-(2-ethylhexyl) phosphate immobilized in the pores of a porous hollow fiber, into a 20-µL acidic aqueous acceptor solution present inside the lumen of the fiber. The parameters influencing electromigration were investigated and optimized. Within 15 min of operation at 200 V, levamisole was extracted from different biological fluid samples with recoveries in the range of 59-65%, which corresponded to preconcentration factors in the range of 118-130. The calibration curves showed linearity in the range of 0.5-10, 0.2-10 and 0.1-10 µg/mL for plasma, urine and saliva, respectively. Limits of detection of 0.1, 0.07 and 0.05 µg/mL and limits of quantification of 0.5, 0.2 and 0.1 µg/mL were obtained for plasma, urine and saliva, respectively. The relative standard deviations of the analysis were found to be in the range of 5.6-9.7% (n = 3). Electromembrane extraction was successfully processed for determination of levamisole in plasma, urine and saliva samples.

A sensitive LC-MS/MS method for determination of levamisole in human plasma: application to pharmacokinetic study.

A sensitive and rapid LC-MS/MS method was developed and validated for the determination of levamisole in human plasma. The assay was based on liquid-liquid extraction of analytes from human plasma with ethyl ether. Chromatographic separation was carried on an Agilent HC-C(8) column (150 mm × 4.6 mm, 5 µm) at 40°C, with a mobile phase consisting of acetonitrile-10 mM ammonium acetate (70:30, v/v), a flow rate of 0.5 mL/min and a total run time of 6 min. Detection and quantification were performed by mass spectrometry in the multiple reaction monitoring mode with positive electrospray ionization m/z at 205.1→178.2 for levamisole, and m/z 296.1→264.1 for mebendazole (internal standard). The assay was linear over a concentration range of 0.1-30 ng/mL with a lower limit of quantification of 0.1 ng/mL. The coefficient of variation of the assay precision was less than 8.5%. The assay was successfully used to analyze human plasma samples in a pharmacokinetic study where levamisole was administered as a liniment.

Overcoming macrocyclic lactone resistance in Haemonchus contortus with pulse dosing of levamisole.

The in vivo effect of dosing levamisole as a pulse release within an ivermectin (IVM) controlled-release device (CRD) was simulated by periodic dosing of levamisole to Haemonchus contortus-infected sheep already treated with an IVM CRD. The rationale for this treatment combination arises from the need to find alternative approaches to the treatment of gastrointestinal parasites in livestock in the face of increasing levels of anthelmintic resistance which is now widespread in Australia. Thirty merino sheep (4 months of age) were infected weekly with a mixture of susceptible and ivermectin resistant H. contortus beginning at Day 28. Twenty eight days after first infection, groups of 10 sheep were treated with IVM capsules alone, IVM capsules and an oral dose of levamisole (LEV) at Days 50 and 100 or no treatment. At pre-determined intervals, up to 126 days after treatment, faecal worm egg counts (FWEC) were determined and development rates of infective larvae (L3) cultured in faeces were measured. Haematological parameters and drug concentration in plasma were measured throughout the 100-day release period of the controlled-release device. Sheep were slaughtered at Day 135 for estimates of total worm burden. FWEC of sheep treated with IVM+LEV declined (99.9% reduction) after administration of oral LEV and were suppressed until Day 98. There was a significant difference (p<0.0001) in worm counts at slaughter between groups. The results demonstrate the potential advantage of combining a pulse of short-acting drug into the long-acting anthelmintic capsule to provide better parasite control than that achieved from the existing CRD treatment when IVM-resistant worms were present.

Pharmacokinetics of levamisole in broiler breeder chickens.

The pharmacokinetics of levamisole was studied in 20 broiler breeder chickens (chickens that give eggs to breed broilers). A single dose of levamisole (40 mg/kg) was administered orally or intravenously to chickens before the onset of egg production, prelay (age = 22 weeks), and repeated at the peak of egg production (age = 32 weeks). A high-pressure liquid chromatographic with ultraviolet detection method (HPLC-UV) was used for quantification of levamisole in plasma. Using compartmental analysis, levamisole followed a three-compartmental open model with mean values of alpha = 0.1224 and 0.4968, beta = 0.01663 and 0.01813, gamma = 0.002 and 0.002/min at the prelay and at the peak of egg production periods, respectively. The mean values for volume of distribution at steady state (V(ss)), determined by compartmental analysis, were significantly different for prelay and peak of egg production (8.358 and 13.581 mL/kg), respectively.

Effect of first-pass hepatic metabolism on the disposition of levamisole after intravenous administration in rabbits.

OBJECTIVE: To evaluate the contribution of first-pass hepatic metabolism of levamisole on levamisole disposition in rabbits. ANIMALS: 30 male New Zealand White rabbits. PROCEDURES: Rabbits were randomly placed into 2 groups. Rabbits in the first group received levamisole via the marginal ear vein at the following 3 doses: 12.5, 16, and 20 mg/kg (5 rabbits for each dose). Rabbits of the second group received levamisole via the jejunal vein at the same doses (5 rabbits each). During the following 240-minute period, plasma samples were obtained and quantified for levamisole concentrations by reversed-phase high-performance liquid chromatography. RESULTS: No significant differences were found between pharmacokinetic parameters calculated by compartmental or noncompartmental analysis. Mean hepatic extraction ratio ranged from -0.044 to 0.017 and from 0.020 to 0.081 when area under the plasma concentration-time curve values were obtained after compartmental or noncompartmental analysis, respectively. After compartmental analysis, plasma concentration decreased bi-exponentially. Mean pharmacokinetic parameter values were as follows for each dose (12.5, 16, and 20 mg/kg, respectively): after levamisole administration via the marginal ear vein, volume of distribution at steady state (Vss) = 4.26, 4.33, and 3.20 L/kg; total body clearance (CI) = 49.04, 43.77, and 39.26 mL/kg x min; and half-life associated with beta-phase (t1/2beta) = 77.93, 85.39, and 69.79 minutes. After levamisole administration via the jejunal vein, Vss = 4.38, 2.85, and 2.97 L/kg; CI = 48.14, 42.40, and 39.69 mL/kg x min; and t1/2b = 101.9, 76.71, and 76.13 minutes. CONCLUSIONS: Levamisole has a low degree of hepatic extraction in rabbits.

Liquid chromatographic method with ultraviolet absorbance detection for measurement of levamisole in chicken tissues, eggs and plasma.

The development and validation of a high-performance liquid chromatographic and UV detection method was accomplished for quantitative determination of levamisole in chicken tissues, eggs and plasma. The chromatographic separation was achieved on Luna 5 microm C(18) column using a mobile phase of 0.2% acetic acid in water:methanol (50:50 (v/v)) and Pic B-7 low UV reagent and the pH was adjusted to 7.31 with ammonium hydroxide and UV wavelength was 225 nm. Limits of quantification were 0.025 microg/g for all tissues and 0.003 microg/ml for plasma. Limit of detection was 0.001 microg/g for tissues and plasma.