Influence of species of negative control sera on results of a brucellosis fluorescence polarization assay.

We evaluated serologic responses of cattle, bison, elk, and swine representing negative control, early vaccination (4-8 wk), late vaccination (21-28 wk) or booster vaccination, early after-experimental challenge (2-4 wk), and late after-experimental challenge (8-21 wk), in a brucellosis fluorescence polarization assay (FPA; n = 10 sera per species per treatment) using negative control sera from cattle, bison, elk, and swine (n = 5 per species). Sera from cattle shedding Brucella abortus strain RB51 in milk were also evaluated against the 20 negative control sera. The species of negative control sera used in the FPA could increase (p < 0.05) delta millipolarization (mP; delta mP = sample mP - negative control mP) results. In general, the species of negative control sera did not alter the interpretation of FPA results in control, vaccinated, or infected animals. Even after repeated RB51 vaccinations in bison, cattle, or elk, or in cattle shedding RB51 in milk, serologic results from the FPA remained negative. Species differences in FPA results were noted; elk developed robust humoral responses very quickly after infection that resulted in strong positive FPA results. In cattle and bison, humoral responses appeared to develop over a longer period of time, and greater delta mP values were detected at later times after infection. Sensitivity of the FPA for detecting infected animals was greatest for elk in early challenge samples and bison in late challenge samples. Our data suggest that species of origin of negative control sera does not influence interpretation of the FPA in natural hosts of Brucella abortus.

Assessment of fluorescence polarization assay: a candid diagnostic tool in Brucella abortus strain 19 vaccinated areas.

Brucellosis caused by the bacteria of the genus Brucella is an important zoonosis and constitutes a serious public health hazard. Brucellosis is diagnosed mainly by the Rose Bengal plate test and indirect ELISA, both of which have poor specificity because false positive serological reactions occur when screening animals that have been vaccinated with B. abortus S19. Fluorescence polarization assay (FPA) was evaluated for screening samples from cattle and buffalo calves with persistent antibody titers induced by vaccination. The standardized FPA exhibited relative sensitivity and specificity of 0.94 and 0.95, respectively, and the area under the curve, kappa and accuracy were 0.98, 0.87 and 0.95, respectively. Comparison of competitive ELISA and FPA revealed that, FPA is more specific than competitive ELISA. The high specificity, sensitivity and 95% accuracy of FPA indicate that, it is suitable for testing vaccinated animals because it can distinguish between infected from vaccinated animals.

Brucella spp. in equines slaughtered in the south region of Brazil / Anticorpos contra Brucella spp. em equídeos da região Sul do Brasil abatidos em matadouro-frigorífico

Bacteria of the genus Brucella are widespread in many countries. These microorganisms can infect humans and many wild and domestic animal species. These bacteria have zoonotic potential, and can cause economic and public health problems since they can be transmitted by direct contact with sick animals, through consumption of contaminated milk, raw meat and its derivatives (Soares et al., 2015). Brucellosis is considered a chronic evolving disease, unusual in horses, predominantly caused by Brucella abortus. However, it is not characterized by reproductive disorders in horses, but primarily by abscess in the cervical region, bursa, tendons, and joints. Transmission is likely to occur via ingestion of contaminated water and pastures, especially in areas endemic for bovine brucellosis (Ribeiro et al., 2008). The slaughterhouse is a strategic point for obtaining information about the animal and animal products, edible or not. This study investigated the presence of anti-Brucella spp. immunoglobulins in the serum samples from horses slaughtered in a slaughterhouse in southern Brazil, to estimate the frequency of Brucella spp. antibodies and determine the spatial distribution of the cases.(AU)

Objetivou-se investigar a presença de imunoglobulinas anti-Brucella spp. em amostras de soros sanguíneos de equídeos abatidos em matadouro-frigorífico, sob Serviço de Inspeção Federal, localizado na região Sul do Brasil. Utilizaram-se 767 amostras de sangue de equídeos adultos abatidos no período de abril a maio de 2013. Os animais foram provenientes de 45 municípios dos estados do Rio Grande do Sul, Santa Catarina e Paraná. Para diagnóstico, foram utilizados os testes do antígeno acidificado tamponado (AAT), sendo os resultados positivos confirmados pelos testes de polarização fluorescente (TPF), reação de fixação de complemento (RFC) e 2-mercaptoetanol (2-ME). Foram sororreagentes no AAT 65 (8,47%) animais. Destes, apenas dois (3,07%) foram positivos também na RFC e três (4,62%) animais foram positivos no TPF. Apesar da baixa frequência de animais positivos para Brucella spp., pode-se afirmar que a infecção em equinos está presente na área estudada, o que é demonstrado pela presença de animais sororreatores. No âmbito da saúde animal, pública e ocupacional, sugere-se a atenção a essa doença, visando diminuir o risco de infecção.(AU)

Field evaluation of three blood-based assays for elk (Cervus canadensis) naturally infected with Mycobacterium bovis.

Diagnosis of Mycobacterium bovis in wild populations is very challenging due to complications imposed by the use of traditional skin tests, poor sensitivity of gold standard tests which rely on culture of M. bovis from tissues and wide variations in severity of disease. Various combinations of a lymphocyte stimulation test (LST), fluorescence polarization assay (FPA) and the Cervid TB Stat-Pak were evaluated using two different validation approaches: a latent class analysis and classical statistical approach using culture as a gold standard. A validation subsample consisting of animals culled for population control and mortalities from capture provided an unbiased estimate of test performance for comparison. The sensitivity of the LST (0.83, 95% CI: [0.70-0.97] as a single test was similar to existing tuberculin skin tests, but the sensitivity of the FPA (0.40, 95% CI: [0.22-0.58]) and Cervid TB Stat-Pak (0.62, 95% CI: [0.41-0.83]) were lower in this population. Test performance of the LST and Cervid TB Stat-Pak in parallel was similar to the use of all three tests in parallel and inclusion of the FPA did not greatly enhance test performance. Prevalence of M. bovis in elk varied substantially between the high risk area of southern Manitoba (9.1%, 95% CI: [6.09-12.1%]) and lower risk areas outside this zone (0.76%, 95% CI: [0-2.26%]). Bayesian latent class analysis indicated lack of covariance between the two antibody tests (FPA and Cervid TB Stat-Pak) while the classical two-stage analysis indicated there was conditional dependence between the tests. All three tests when used in parallel resulted in 100% NPV using all three validation methods, indicating few elk were misclassified as false negative by post mortem culture. Similar to previous studies, this study found that combinations of blood tests that utilize cell mediated responses along with humoral antibody responses maximize the sensitivity of tests for diagnosis of M. bovis in wild cervid populations.

Evaluation of the fluorescence polarization assay for the detection of Brucella abortus antibodies in bison in a natural setting.

Bison and elk in the greater Yellowstone area are the last-known reservoir of Brucella abortus in the United States. Diagnosis of brucellosis is challenging as there is no perfect reference test. The objectives of this study were to estimate the accuracy of the fluorescence polarization assay (FPA) for the screening of B. abortus antibodies in bison in a natural setting. Serum and tissue samples were collected and analyzed from the known brucellosis-infected bison herd in Yellowstone National Park (YNP). Additionally, serum samples from privately owned bison were serologically tested for brucellosis. While the FPA and five other tests had perfect sensitivity, all tests had substantially lower specificity in the YNP herd. However, a Bayesian analysis showed that as many as 59-74% of the culture-negative animals were most-likely truly infected. A decision-tree analysis showed that the expected cost of FPA testing was comparable to the cost of other serologic tests. The FPA was shown to be highly sensitive but may not be able to differentiate culture-positive and culture-negative animals. There is a need for long-term longitudinal studies to estimate diagnostic accuracy of tests for B. abortus in bison.

Effect of the water-soluble fraction of petroleum on microsomal lipid metabolism of Macrobrachium borellii (Arthropoda: Crustacea).

The effect of the water-soluble fraction of crude oil (WSF) on lipid metabolism was studied at critical metabolic points, namely fatty acid activation, enzymes of triacylglycerol and phospholipid synthesis, and membrane (lipid packing) properties in the freshwater prawn Macrobrachium borellii. To determine the effect of the contaminant, adults and embryos at different stages of development were exposed to a sublethal concentration of WSF for 7 days. After exposure, microsomal palmitoyl-CoA synthetase (ACS) showed a two-fold increase in adult midgut gland. Embryo's ACS activity was also affected, the increment being correlated with the developing stage. Endoplasmic reticulum acylglycerol synthesis was also increased by WSF exposure in adults and stage 5 embryos, but not at earlier stages of development. Triacylglycerol synthesis was particularly increased (18.5%) in adult midgut gland. The microsomal membrane properties were studied by fluorescent steady-state anisotropy, using the rotational behavior of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Microsomes from midgut gland of WSF-exposed prawn showed no differences in fluidity. Nevertheless, microsomes incubated with WSF in vitro increased their fluidity in a temperature- and WSF concentration-dependent fashion. Both, aliphatic and aromatic hydrocarbons individually tested elicited an increase in membrane fluidity at 10 mg/l, but at 4 mg/l only nC10-C16 aliphatics did. In vivo results indicate that WSF increased the activity of microsomal enzymes that are critical in lipid metabolism, though this change was not due to direct alterations in membrane fluidity, suggesting a synthesis induction, or an enzyme-regulatory mechanism. Nevertheless, hydrocarbons elicited membrane fluidity alterations in in vitro experiments at concentrations that could be found in the environment after an oil spill.

Experimentally induced monensin-resistant Eimeria tenella and membrane fluidity of sporozoites.

Two resistant lines of Eimeria tenella (H) to monensin were developed after 35 passages in chickens medicated with 100-125 ppm or 125-200 ppm monensin in the diet. Drug sensitivity of the induced lines to different level drugs were estimated with mean lesion scores (LS), mean oocyst productions (OP), percentage optimum anticoccidial activity (POAA), reduction of lesion scores (RLS), relative oocyst production (ROP), anticoccidial index (ACI) and global index (GI), respectively. Membrane fluidity of sporozoites of the sensitive line (i.e. the parent line, coded as MON-S((S))) and two resistant lines (coded as MON-R((S))-1 and MON-R((S))-2) with and without in vitro exposure to monensin were determined. Membrane fluidity of MON-R((S))-1 and MON-R((S))-2 were significantly lower than that of MON-S((S)). In vitro exposure to monensin significantly increased membrane fluidity of MON-S((S)), but had a much less effect on those of MON-R((S))-1 and MON-R((S))-2. Sporozoits of the MON-S((S))and MON-R((S))-2 with or without in vitro exposure to monensin were examined by SEM, and the sensitive sporozoites (MON-S((S))) appeared swollen and bulgy after treatment with monensin, while there was no obvious morphological deformation in the resistant sporozoites (MON-R((S))-2). The results suggest that the altered membrane fluidity in the membranes of E. tenella may be related to the decreased sensitivity to monensin.

Comparison of fluorescence polarization assay with card and complement fixation tests for the diagnosis of goat brucellosis in a high-prevalence area.

An evaluation of fluorescence polarization assay (FPA) to detect antibodies against Brucella melitensis according to the Mexican Official Norm (NOM) was performed. In this study, a total of 2582 goat serum samples from a high-prevalence area in northeast Mexico where vaccination is applied, were used. Of these, 1094 were classified as NOM negatives (card test (CT) negatives or CT positives/complement fixation test (CFT) negatives) and 1488 as NOM positives (CT and CFT positives). The receiver operator characteristics (ROC) curve analysis was used to obtain the FPA sensitivity (83.5%), specificity (82.2%) and accuracy (88.2%) compared with NOM criteria, using a cut-off value of 89mP for positive samples. In addition, FPA produced 84.1% of negative results versus 65.7% of CT using 1094 CFT negative samples, which indicated that FPA performance was better than CT to detect negative samples or differentiate samples from vaccinated animals. Finally, FPA showed 95.8% sensitivity when using 702 negative non-vaccinated samples. Taken together, these results suggested that FPA might replace CT as a screening test for its better performance compared with CFT, its adjustable cut-off useful in different epidemiological situations, and for its reliability, ease of performance, comparable cost with CT regimen, and potential application in field and high-throughput laboratories. The use of FPA as screening test will help to reduce the percentage of goats wrongly slaughtered because of brucellosis misdiagnosis. More studies on FPA are required for its approval as diagnostic tool for goat brucellosis.

Measurement of protease activity of live Uronema marinun (Ciliata: Scuticociliatida) by fluorescence polarization.

The proteolytic activity of live Uronema marinum was analyzed by a fluorescence polarization (FP) technique. Protease activity was measured as a decrease in the FP value using fluorescein isothiocynate (FITC)-casein as a protein substrate. A time-dependent decrease in FP occurred in plate wells containing live U. marinum. Supplementation with the cysteine protease inhibitor E-64 had no significant inhibitory effect on the decrease in FP at any of the concentrations used. In contrast, supplementation with 1,10-phenanthroline resulted in complete inhibition of proteolysis for 30 min at 1 mM and for 1 h at 2 and 5 mM. Effective inhibition of the proteolytic activity of live U. marinum by 1,10-phenanthroline indicated that metalloproteases are the main proteases excreted by U. marinum. As U. marinum has a high potential for systemically invading and destroying fish tissues, the metalloproteases excreted by live U. marinum are likely to be involved in the invasion of host tissues and the pathogenicity of the parasite.

Detection of Salmonella enteritidis in incubated pools of egg contents by fluorescence polarization and lateral flow immunodiffusion.

Efficient detection of Salmonella enteritidis inside eggs is critical for confirming that individual commercial laying flocks present a risk to public health. In most standard bacteriological culturing protocols, an initial incubation step is necessary to allow the typically very small population of S. enteritidis cells in pools of egg contents to multiply to more easily detectable levels. In the present study, two rapid methods were evaluated as alternatives to plating on selective media for detecting S. enteritidis in incubated egg pools. By using either fluorescence polarization or lateral flow immunodiffusion assays, S. enteritidis could be consistently detected in egg pools at 10(8) cfu/mL (and in most pools at 10(7) cfu/mL). Although the rapid assays were significantly less sensitive than culturing, they both were consistently able to detect contamination when pools of 10 eggs were inoculated with approximately 10 cfu of S. enteritidis and incubated for 72 h at 25 degrees C.

Regional differences in transport, lipid composition, and fluidity of apical membranes of small intestine of chicken.

Na+-dependent D-glucose transport was studied in brush-border membrane vesicles from duodenum, jejunum, and ileum of 5- to 6-wk-old chickens. Regional differences were found, and both initial rates and accumulation ratio of D-glucose were higher in the proximal part of the small intestine than in the ileum. To establish the mechanism(s) underlying these differences we have studied the density of Na+-dependent D-glucose cotransporter (SGLT1) as well as lipid composition and fluidity. Phlorizin-specific binding and Western blot analysis indicated a decrease in the amount of SGLT1 in the ileum when compared to the duodenum and jejunum. The distal part of the small intestine also showed a decrease in free cholesterol content and saturated-to-unsaturated fatty acid ratio together with an increase in lipid content and phosphatidylcholine-to-sphingomyelin ratio. These results were associated with a decrease in the diphenylhextriene fluorescence polarization found in brush-border membranes of the ileum. We can conclude that the decrease in the apical D-glucose transport found in the ileum is primarily due to a reduction in the amount of SGLT1 present in the brush-border membrane rather than the differences in the lipid composition and fluidity.

Fluorescence polarization assay for the diagnosis of bovine brucellosis: adaptation to field use.

A fluorescence polarization assay (FPA) was used to test whole blood samples prepared by mixing blood cells from cattle without exposure to Brucella abortus (B. abortus) with sera from animals with confirmed (bacteriologically) infection. A cut-off value between negative and positive values was initially established to be 87.2mP. This value was changed to 95mP to increase assay specificity without loss of sensitivity when testing blood samples from negative animals. The FPA technology was applied to whole blood samples in the field and to stored whole blood samples using two diluent buffers. Relative sensitivity and specificity values for the FPA performed in the field, based on buffered antigen plate agglutination test and competitive enzyme immunoassay results were 95.3 and 97.3%, respectively. However, to obtain maximum sensitivity and specificity, a cut-off value of 105mP was determined for fresh whole blood samples. The relative sensitivity and specificity values of the FPA when testing stored whole blood samples were 100% each using a 95mP cut-off.The usefulness of the FPA for testing whole blood samples in the field was demonstrated.

Evaluation of the fluorescence polarization assay and comparison to other serological assays for detection of brucellosis in cervids.

The complement fixation test (CFT), competitive enzyme immunoassay (CELISA), indirect enzyme immunoassay (IELISA) and fluorescence polarization assay (FPA) were evaluated for the detection of antibodies to Brucella abortus and Brucella suis biotype 4 in caribou (Rangifer tarandus caribou), elk (Cervus elapus), red deer (Cervus elapus), and reindeer (Rangifer tarandus tarandus). When combining the data the FPA and the CELISA were determined to be the most suitable tests for serodiagnosis of Cervidae. The overall actual sensitivity of the CFT and the IELISA was 100%. The overall actual sensitivity for the CELISA and FPA was 99%. The overall relative specificity of the CFT (including treatment of anti-complementary data as positive or negative for analysis), the CELISA, the IELISA and the FPA were 65%, 93%, 99%, 99%, and 99%, respectively. The specificities of the buffered plate agglutination test (BPAT), the CFT, the CELISA, the FPA and the IELISA for 55 elk vaccinated with B. abortus strain 19 and tested 4 mo post vaccination were 14%, 31%, 51%, 84%, and 2%, respectively. The FPA is the diagnostic test of choice because it has sensitivity and specificity values comparable to the CELISA; it has the capability to distinguish vaccinal antibody and antibody resulting from exposure to cross-reacting organisms such as Yersinia enterocolitica 0:9 from antibody to Brucella spp. in most cases; it is technically simple to do; it is adaptable to field use and it is relatively inexpensive.

Modulation of anthracycline activity in canine mammary tumour cells in vitro by medroxyprogesterone acetate.

Failure of chemotherapy with anthracyclines as a result of drug resistance and toxicity is a major problem in the clinical management of neoplasia. The aim of the present study was to evaluate the activity of medroxyprogesterone acetate (MPA) as a chemosensitiser on anthracycline cytotoxicity. The study investigated whether such an effect could be related to an increase in lipid peroxidation, nitric oxide production, membrane fluidity and intracellular anthracycline concentration. The results showed that anthracyclines decreased nitric oxide production but increased membrane viscosity (polarisation constant) and lipid hydroperoxide formation in canine mammary tumour cells. Moreover, it was found that both drug-induced cytotoxicity and membrane viscosity increased in the presence of MPA. Conversely, lipid hydroperoxides decreased in MPA-supplemented cells. Medroxyprogesterone acetate did not show any effect on nitric oxide production. The two anthracyclines used (doxorubicin and idarubicin) showed differential intranuclear accumulation in canine mammary tumour cells, and MPA significantly modified intracellular concentration of anthracyclines.

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.

Diagnosis of bovine brucellosis using a homogeneous fluorescence polarization assay.

To evaluate the fluorescence polarization assay (FPA) for the serological diagnosis of bovine brucellosis, 118 sera from cattle which were culture positive for Brucella abortus, 1751 sera from cattle from premises containing cattle infected with B. abortus, 1222 sera from cattle vaccinated with B. abortus strain 19 and 1199 sera from cattle with no evidence of brucellosis were tested in Argentina, Chile, Mexico and in the American states of Iowa, Missouri and Texas. Initial determination of serological positivity and negativity was based upon reactivity in currently used serological tests, consisting of a rapid screening test, the rose-bengal or the buffered plate antigen tests, followed by a second serological test, the complement fixation test. Sensitivity of the FPA (sera from culture positive animals) ranged from 87.5% to 100%. Serological positivity of cattle from infected premises ranged from 65.5% to 99.0% while the % negative cattle in herds without evidence of brucellosis was between 94.9 and 100%. Of B. abortus strain 19 vaccinated cattle which were positive in at least one in-use serological tests, 88.2% were negative in the FPA. In contrast, previous Canadian studies, sensitivity values were 99.0% and 100% and the specificity in both cases was 100%. This discrepancy was probably due to the use of less well characterized sera in the current study.

Gentamicin pharmacokinetics in newborn and 42-day-old male piglets.

The pharmacokinetics of gentamicin was investigated in six newborn male piglets, aged from 4 to 12 h at the time of administration of the drug, and six 42-day-old castrated male piglets, that had been weaned for 2 weeks following a single intravenous bolus of 5 mg/kg. Gentamicin was measured in serum and in urine by a fluorescence polarization immunoassay. The serum concentration-time data were best described by a three-compartment open model. A rapid initial distribution phase (pi phase) was observed in every animal. The serum beta half-life (t 1/2 beta) was significantly longer in the newborn piglets (mean +/- SEM) (5.19 +/- 0.30 h) than in the older group (3.50 +/- 0.23 h) (P < 0.05). Mean residence time was similarly longer in younger piglets (6.62 +/- 0.57 h) than in older animals (2.86 +/- 0.11 h) (P < 0.05). The steady-state volume of distribution (Vdss) was significantly larger for younger pigs (0.785 +/- 0.036 L/kg) than in elder pigs (0.474 +/- 0.029 L/kg) (P < 0.05). Urinary gamma half-life (t 1/2 gamma u) was 72.66 +/- 10.78 h in the newborn piglets and 69.20 +/- 14.77 h in the 42-day-old animals. A urinary delta phase was observed in three of the 42-day-old piglets and gave a mean t 1/2 delta u of 232.01 +/- 14.55 h. Percentages of urinary recovery of the administered dose after 144 h were 94.18 +/- 1.01 and 94.04 +/- 1.12 in the newborn and 42-day-old animals, respectively. Serum gentamicin clearance was significantly lower in younger animals (0.121 +/- 0.007 L/h.kg) than in the 42-day-old group (0.166 +/- 0.010 L/h.kg). It is suggested that in the newborn piglets, the increase of Vd(SS) could be explained by a higher proportion of extracellular water while the lower clearance could be attributed to a reduced glomerular filtration capacity. Gentamicin dosage requirement in the newborn piglets would therefore have to be adjusted, in order to take into consideration the observed differences in the man values of these latter pharmacokinetic parameters.

Lidocaine elimination and monoethylglycinexylidide formation in the dehydrated camel.

The elimination kinetics and the formation of the monoethylglycinexylidide (MEGX), a major metabolite of lidocaine, were studied in camels deprived of water for 14 days. The study was conducted on four camels in a crossover design. Lidocaine was administered intravenously at a dose of 1 mg/kg to adult female camels when water was given ad libitum (stage 1) and to the same camels after 14 days of dehydration. Blood samples were taken up to 6 h after dosing. Serum lidocaine and MEGX levels were analysed by polarization fluorescence immunoassay. The elimination profiles of lidocaine and the formation of the metabolite MEGX in the two phases of the study were essentially identical. No difference in any pharmacokinetic parameter was noticed between normally hydrated and water-deprived camels. It is thus concluded that dehydration does not affect the cytochrome P450 isozymes involved in degradation of lidocaine to MEGX nor does it affect the hepatic blood flow, which is a major determinant in the clearance of lidocaine. The very low clearance of lidocaine in the camel in comparison with other ruminant or monogastric mammals may be associated with the camel's ability to survive drought in the desert.