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It is of great importance to detect chlorotetracycline (CTC) in a highly sensitive and specific way because of its wide distribution in aquaculture and animal husbandry. Herein, we propose a novel ratiometric fluorescence strategy to assay CTC by using bovine serum albumin stabilized gold nanoclusters (BSA-AuNCs). The BSA-AuNCs consisting of 25 gold atoms (Au 25 NCs) display a red emission at 640 nm (λ ex  = 370 nm). In the presence of CTC, a new blue emission at 425 nm is emerged and its intensity dramatically increases with the addition of more the analyte; meanwhile the red emission at 640 nm shows a linear decrease reversely. However, at identical conditions neither the analogues of CTC as tetracycline (TC), oxytetracycline (OTC) or doxycycline (DC) induces similar response of BSA-AuNCs. Such interesting phenomenon is proven related to the conversion from large Au 25 NCs to smaller nanoclusters composing 8 gold atoms (Au 8 NCs), which intrinsically originate from the interaction between CTC and the ligand BSA. Therefore, a ratiometric probe is established to sensitively detect CTC in the wide range (0.2-10 μM) with a low limit of detection (LOD) at 65 nM. In addition, this strategy can also be applied to assay CTC in human serum, showing great promise for practical applications in future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chlortetracycline is (CTC) is a tetracycline antibiotic which is being in the white-tailed deer industry to improve production and animal health. In this paper, we present a method for determining chlortetracycline residues in edible white-tailed deer tissues, using liquid chromatography with heated electrospray ionization and mass spectrometry detection. The procedure involved extraction with EDTA-McIlvaine buffer at pH 4.0, followed by solid-phase extraction cleanup using a hydrophilic-lipophilic balance (HLB) cartridge. The liquid chromatography analysis was performed with heated electrospray ionization and mass spectrometry detection. The limit of quantification for the method was 2.7 ng/g and limit of detection was 0.8 ng/g. The recovery values were >78.5% for muscle, 65.1% for kidney, 63.1% for liver. Mean tissue residue concentration of chlortetracycline and it's epimer, 4-epi chlortetracycline (4-epi-CTC) at 10-day withdrawal period for kidney, liver, muscle was 122.8, 44.7 and 26.7 ng/g, respectively. Chlortetracycline tissue residue concentration at 45-day withdrawal period for kidney, liver, muscle was 19.2, 28.9 and 10.7 ng/g, respectively. Mean tissue concentration of CTC was less than the established maximum residual limit (MRL) values for bovine tissues. We have validated and successfully applied this method in the qualitative and quantification of chlortetracycline in white-tailed deer tissue samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The purpose of this study was to determine if concentrations of chlortetracycline could be detected in fetal plasma or tissues after administering an oral dose of chlortetracycline (CTC; 500 mg/head/day) reported to be effective in controlling Campylobacter spp. abortions. Five pregnant ewes were administered 250 mg/head twice a day (total dose 500 mg/hd/d) for 7 days. On the beginning of day 7, intravenous catheters were surgically implanted or inserted into the fetus and dam. Plasma samples were collected from the ewe and fetus at various time points before and up to 36 hr after the last dose of CTC. All ewes were then sacrificed, and tissues were harvested from the fetus for drug analysis. Concentrations of CTC in maternal plasma were consistent with our previous study and below the minimum inhibitory concentration of Campylobacter abortion isolates. Concentrations of CTC were below the limit of detection in three of five fetal plasma samples and all of the placenta, amniotic fluid, and fetal stomach contents. Low concentrations were detectable in fetal kidney and liver, suggesting that CTC reaches the fetus, although at a variable and low ratio when compared to maternal concentrations., (© 2017 John Wiley & Sons Ltd.)

Fifteen parturient camels given chlortetracycline (CTC) as intrauterine pessaries (3 g/head) were divided into the control group (n = 5), which remained untreated, oxytocin-treated group (50 IU, intramuscular; n = 5), and cloprostenol-treated group (Estrumate, 500 μg, intramuscular; n = 5). Serum samples were collected at 0, 1, 2, 4, 8, 24, 48, and 72 hours after treatment and CTC was determined. The CTC appeared in blood within 1 hour. The maximum concentration of CTC was detected in blood after 72 (543.58 ± 117.85 μg/L), 8 (520.48 ± 13.65 μg/L), and 1 hour (831.98 ± 111.01 μg/L) of administration in control, oxytocin-, and PGF2α-treated camels, respectively. There was a high significant effect of time (P < 0.001) and treatment-by-time interaction (P < 0.001) on serum CTC concentration. In the control group, there was a significant (P < 0.05) increase in CTC concentrations at 72 hours compared to the other times. In the oxytocin group, there was a significant (P < 0.05) decrease in CTC concentrations at 24, 48, and 72 hours compared to its level after 1 or 8 hours. In PGF2α, there was a significant (P < 0.001) decrease in CTC concentrations at 2, 4, 8, 24, 48, and 72 hours compared to its level after 1 hour. Treatment contrast at different time points showed a significant (P < 0.001) increase in CTC concentration after 1 hour in the PGF2α-treated group compared to oxytocin and control groups. By 72 hours, CTC concentrations were significantly (P < 0.05) lower in PGF2α and oxytocin groups than in the control group. In conclusion, serum CTC concentration in dromedary camels increases within 1 hour after intrauterine administration and remains elevated for at least 72 hours in control, oxytocin-, and PGF2α-treated animals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of feed-grade chlortetracycline (CTC) in sheep after oral administration of 80 or 500 mg/head daily, divided into two equal doses given at 12-h intervals for 8 days. These are the approved, and commonly used but unapproved, feed additive doses, respectively, in the United States for the prevention of ovine infectious abortion. Blood samples were collected just prior to dosing at 0, 12, 24, 72, 96, and 192 h, as well as 4, 8, 12, 24, and 36 h after the last dose, and noncompartmental pharmacokinetic analysis was performed to estimate elimination half-life and area under the plasma concentration-time curve (AUC). Mean observed maximum CTC concentrations (Cmax ) were 20.0 ng/mL (80 mg dose) and 101 ng/mL (500 mg dose). Mean apparent elimination half-life was 18 h (80 mg dose) and 20 h (500 mg dose). Although published data do not exist to estimate plasma CTC concentrations necessary for the prevention of ovine infectious abortion, concentrations reached in our study suggest that either the FDA-approved and FDA-unapproved dosages are not high enough or that the pharmacodynamic parameter relating preventive dose to pathogen minimum inhibitory concentrations is yet to be determined., (© 2014 John Wiley & Sons Ltd.)

Chickens were used to investigate plasma disposition of chlortetracycline after single IV (15 mg/kg) and multiple oral administration (60 mg/kg, 5 days) and residue depletion of chlortetracycline after multiple oral doses (60 mg/kg, 5 days). Plasma and tissue samples were analyzed by HPLC. Mean elimination half-lives in plasma were 7.96 and 13.15 h after IV and multiple oral administration. Maximum plasma concentration was 4.33 μg/ml and the interval from oral administration until maximal concentration was 1.79 h. Oral bioavailability was 17.76%. After multiple oral dose, mean kidney, liver and muscle tissue concentrations of chlortetracycline+4-epi-chlortetracycline of 835.3, 192.7, and 126.3 μg/kg, respectively, were measured 1 day after administration of the final dose of chlortetracycline. Chlortetracycline residues were detected in kidney and liver (205.4 and 81.7 μg/kg, respectively), but not in muscle, 3 days after the end of chlortetracycline treatment. The mean chlortetracycline+4-epi-chlortetracycline concentrations were below LOQ at 3 and 5 days after cessation of medication in muscle and liver, respectively. A withdrawal time of 3 days was necessary to ensure that the chlortetracycline residues were less than the maximal residue limits (MRLs) established by the European Union (100, 300, and 600 μg/kg in muscle, liver, and kidney, respectively)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Chlortetracycline HCl (CTC) has impacted profitable livestock production since 1945. However, pharmacokinetic parameters for CTC in ruminating cattle are unavailable in peer-reviewed literature. A total of 18 steers were randomized to 4.4, 11, or 22 mg/kg/day p.o. CTC treatment groups (n = 6). Chlortetracycline treatment was offered as one-half of the daily dose b.i.d. (160 total doses/group) for 80 days. Blood samples were collected at selected time points throughout an 83-day study and analyzed with a solid phase extraction technique and novel ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy analytical method. Noncompartmental analysis (NCA) determined individual pharmacokinetic parameters by treatment group with coefficient of variation (CV %) estimates. A one-compartment open model with first order absorption and elimination, where absorption rate constant was equal to elimination rate constant, was fitted using nonlinear mixed effects modeling (NLMEM). NLMEM determined the primary pharmacokinetic parameters: volume of distribution (V/F, 40.9 L/kg) and rate constant (k, 0.0478 h(-1)), and the secondary parameters: dose-normalized area under the curve (AUC/D, 0.29 h x microg/L), clearance (Cl/F, 1.8 L/kg/h), elimination half-life (t(1/2), 16.2 h), C(max/Dose) (4.5 ng/mL), and time of C(max) (T(max), 23.3 h) with improved CV estimates over NCA. Dose linearity was confirmed by anova of parameters derived from NCA by treatment group. Further studies are necessary for determining absolute bioavailability and pharmacokinetic-pharmacodynamic relationships of CTC in group fed, ruminating cattle.

Chlortetracycline (CTC) is a member of the group of the tetracycline antibiotics used in human and veterinary medicine. Its reliable measurement in plasma - necessary to study its pharmacokinetics - is hampered by the fact that CTC is subjected to keto-enol tautomerism resulting in its keto- and enol-form. Also, it undergoes epimerization to form its 4-epimer. In this paper, we present an LC-ESI-MS/MS method to analyze the CTC content in animal plasma, with the originality that it apports a solution to overcome the possible interference of the keto-enol tautomerism equilibrium, which is influenced by several factors. Therefore, the plasma samples were incubated at 56 degrees C, forcing the equilibrium completely in favour of the CTC keto-form. The CTC keto-tautomer was stable after deproteinization of the samples with concentrated trifluoroacetic acid, and was quantified by LC-ESI-MS/MS, as a measure of the total CTC content. The method could be validated for pig and chicken plasma by a series of parameters - linearity, trueness, precision, limit of quantification, specificity, stability - in accordance with the European guidelines, and was used for pharmacokinetic studies on pigs and chickens medicated with CTC via the feed.

A rapid, selective and sensitive method has been developed for the determination of chlortetracycline in swine plasma by LC-ESI/MS/MS. The method consists of a protein precipitation extraction for sample preparation and liquid chromatography ionspray tandem mass spectrometry for analysis. The plasma samples were extracted with acetonitrile and the supernatants were analyzed using an LC-ESI/MS/MS instrument. Separation was achieved using a C(8) analytical column and an isocratic mobile phase composed of 70:30 acetonitrile:0.5% formic acid in water at a flow rate of 500 microL/min. A linear (weighted 1/concentration) relationship was used to perform the calibration over an analytical range 20--2000 ppb (ng/mL). The intra-batch precision and accuracy at LLOQ, medium and high concentrations were 9.0, 11.3 and 9.9% and 97.7, 100.3 and 98.4%, respectively, and the inter-batch precision and accuracy at LLOQ, medium and high concentrations were 9.1, 8.4 and 7.4% and 95.1, 102.1 and 97.1%, respectively. This LC-ESI/MS/MS method for the determination of chlortetracycline in swine plasma has been proven to be within generally accepted criteria used for bioanalytical assay., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

A highly selective method of chlortetracycline (CTC) is proposed on the basis of the measurements of total internal reflected resonance light scattering (TMR-RLS) at water/tetrachloromethane (H20/CCl4) interfaces. In the pH range of 7.54-8.14, the interaction of the binary complex of Eu(III)/CTC in the presence of trioctyl phosphine oxide (TOPO) occurs at the H20/CCl4 interface, resulting in greatly enhanced TIR-RLS signals with the maximum peak located at 340 nm. The enhanced TIR-RLS intensity is in proportion to the CTC concentration in the range 0.98 to approximately 20.0 x 10(-7) mol/L. The limit of detection is 9.8 x 10(-9) mol/L. Synthetic samples and body fluid samples including human urine, human serum, and fresh milk were determined with the recovery of 95.4-106.4% and RSD of 2.9-3.9%.

Various seed diets containing chlortetracycline were fed to large and small parrots to evaluate serum chlortetracycline concentrations. The substitution of dehulled sunflower seed for whole sunflower in the seed mix may have resulted in higher chlortetracycline concentrations in cockatoos and parrots. The serum chlortetracycline concentration achieved for all diets was less than the goal of 1 microgram/mL, but the concentrations attained may be useful for therapy.

The fluorescence system of Eu-chlortetracycline-TOPO-sodium dedecyl sulfonate was studied. It was found that chloretetracycline formed a complex with Eu(III) at pH 8.0-9.0 and then emitted the characteristic fluorescence of Eu(III). TOPO and sodium dodecyl sulfonate greatly enhanced the fluorescence intensity of the system. The experiments indicated that under the optimum determining conditions a linear relationship was obtained between the fluorescence intensity and chlortetracycline concentration in the range of 2.0 x 10(-8)-1.0 x 10(-5) M. The detection limit was 6.0 x 10(-9) M. In addition, the luminescence mechanism of the complex system has been discussed.

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.

Sera obtained from pigs before and after subtherapeutic levels of ASP250 supplementation (pre and post serum pools) have been subjected to comparative fractionation by using gel filtration and affinity chromatography on immobilized Cibacron Blue F3G-A. Comparable serum fractions obtained from pre- and post-ASP250 blood sera were assayed in muscle cell culture bioassays designed to measure their effect on proliferation. Pre- and post-ASP250 sera were subjected to gel filtration and divided into the following fractions: fraction 1, Kav less than .17; fraction 2, Kav = .17 to .41; fraction 3, Kav = .41 to .59. Post-ASP250 fractions 2 and 3 increased proliferation rate in cultured muscle cells to a greater extent than comparable pre-ASP250 fractions (P less than .001). Chromatography of fraction 3 on immobilized Cibacron Blue F3G-A showed that both pre- and post-ASP250 fraction 3 contained a putative inhibitor of myogenic cell proliferation as well as mitogenic factors. However, negative growth factor activity was greater in pre-ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05). Additionally, positive growth factor activity was lower in pre-ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05). These data suggest that levels and(or) activities of both positive and negative muscle growth factors in serum may be altered by the addition of antimicrobials to the diets of growing pigs.

Chlortetracycline hydrochloride was administered intra-arterially (11 mg/kg) and as an oral drench (33 mg/kg) to ten 21.0-31.5-kg pigs. Five of the pigs were fasted 18 h prior to dosing and five of the pigs were fed ad libitum prior to dosing. The mean volume of distribution determined by area-under-the-curve calculations for the fasted pigs (0.967 +/- 0.210 l/kg) was significantly less (P less than 0.05) than the mean volume of distribution for the fed pigs (1.39 +/- 0.31 l/kg). Mean total body clearance of the drug was also significantly less (P less than 0.05) in the fasted pigs (0.165 +/- 0.055 l/kg/h) as compared to the fed pigs (0.307 +/- 0.053 l/kg/h). The elimination constants (beta) were not found to be statistically different (P less than 0.05): 0.1811 +/- 0.0057 for the fasted pigs; 0.2260 +/- 0.0461 for the fed pigs. The bioavailability for both groups was similar; 19.12 +/- 8.3% for the fasted pigs and 17.88 +/- 5.3% for the fed pigs. In a second experiment three groups of six pigs which weighed 34.5-44.1 kg were fed a corn-soy diet ad libitum. The rations were fortified with chlortetracycline at 100, 400 or 1000 mg chlortetracycline hydrochloride/kg feed. Chlortetracycline concentrations were determined in plasma samples collected over a 6-day period. Plasma chlortetracycline concentrations reach a plateau within 24 h after initial access to the trial diets and were highly correlated with the dose of the drug consumed (r2 = 0.97).

Plasma and tissue concentrations, following the oral administration of the antibiotic chlortetracycline (CTC) alone or with citric acid, were determined in healthy and infected (Pasteurella multocida) turkeys. The principal results were: 1) The dose (of CTC) versus plasma level relationship was nearly linear. 2) Addition of citric acid to an oral preparation produced significantly higher plasma levels when divalent cations Ca2+ (.3 g/liter) and Mg2+ (.1 g/liter) were present in the drinking water and dosage solution than when citric acid was omitted. 3) The concentration of CTC was considerably higher in the liver and kidney than in the muscle and brain. 4) Birds infected with P. multocida had significantly higher plasma levels than healthy birds. 5) Oral administration of CTC increased the survival rate of the birds infected with P. multocida.

Three experiments were conducted to compare different methods of short-term potentiation of tetracycline antibiotics for broiler chicks. Reduction of dietary calcium and addition to sodium sulfate were compared in different combinations with various levels of chlortetracycline (CTC) and oxytetracycline (OTC). Reducing dietary calcium from 0.8 to 0.4% significantly increased serum levels of CTC and OTC. Adding sodium sulfate (1.25%) also increased serum levels; the majority of the response occurred at the higher calcium level. There was no benefit from adding sodium sulfate to the low-calcium diet. Neither body weight gain nor feed utilization were adversely affected during the 5-day test period.

The pharmacokinetics of chlortetracycline (CTC) in plasma and bile after intravenous administration in turkeys was ascertained. After a dose of CTC (0.9 mg/kg) was administered IV, 8.5% of the dose appeared in the bile in 4 hours. The peak bile/plasma concentration ratio for CTC was 254 at 2 hours. The bile/plasma concentration ratio was greater than 1 from 10 to 240 minutes after CTC administration.

The biological availability of chlortetracycline oral preparations used in veterinary biovit-80, biovetin and chlortetracycline) was studied on pigs. It was found that a single administration of biovit-80 or biovetin in a dose of 25,000 units kg of the body weight calculated for the chemically pure antibiotic did not provide sufficiently high therapeutic levels of the antibiotic in the blood of the pigs. The dose of biovetin biologically equivalent to 25,000 units/kg of chlortetracycline hydrochloride was 62 500 units/kg and exceeded the recommended one by 2.5 times, while equivalent dose of biovit-80 exceeded the recommended one by more than 2.5 times.

Chlorotetracycline has been used in neutrophils and other cells as probe of the state of membrane-bound calcium. We report here that human neutrophils treated with chlorotetracycline response to soluble secretagogues by a prompt decrease in chlorotetracycline fluorescence. This response was observed within 2-5 s, making it one of the most immediate reactions in neutrophils to stimulation, and was obtained with three secretagogues studied: a chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, a tumor promotor (phorbol myristate acetate) and a lectin (concanavalin A). The responses of neutrophils to the three stimuli differed both quantitatively and qualitatively. The calcium EGTA, did not effect the onset of the decrease in chlorotetracycline fluorescence, suggesting that the probe was measuring changes in intracellular calcium pools. The intracellular calcium antagonists, TMb-8, W-7 and trifluoperazine, did not block, but actually augmented, the fluorescence response. All four of these calcium antagonists blocked the recovery of chlorotetracycline fluorescence which was usually observed several minutes after stimulation with N-formyl-methionyl-leucyl-phenylalanine. This suggests that recovery was dependent upon both extracellular calcium and active calmodulin. The results are consistent with the hypothesis that changes in chlorotetracycline fluorescence reflect changes in a pool of membrane-bound 'trigger calcium', the release of which is an essential first step in stimulus-response coupling in human neutrophils.

The bioavailability of oxytetracycline (OTC) and chlortetracycline (CTC) was studied in non-fasting calves. The availability of OTC was found to be 5% and of CTC 37% after oral administration of 10 mg/kg. The availability was reduced when the drugs were given in a milk replacer or in cow's milk. The area under curve (AUC) was reduced 68% when OTC was given in milk replacer, the reduction of CTC availability was 40%. In milk the reduction was 72% for OTC and 47% for CTC. Calcium and iron caused a dramatic reduction of the serum levels. OTC was stored mixed in milk powder at room temperature for 6 months without loss in availability. OTC did not chelate calcium ions in serum. The conclusion drawn from the results was that CTC is more suitable than OTC for oral therapy in calves.

Avian chlamydiosis remains to be an important, in birds widely spread zoonosis. In the past 15 years in the Federal Republic of Germany 6133 cases in birds or aviaries officially were recorded, 88% in aviaries consisting of psittacines, 9% in pigeons and 3% in other bird species. Among all bird species psittacines are of greatest importance for human health. Therefore, public health control measures must concentrate on these species. For this purpose the longterm-treatment with tetracyclines in feed or by intramuscular injection has proved effective since chlamydial agents perfectly can be eliminated. But control of psittacosis by medication in the hands of laymen is problematical. Effectivity of medication depends on proper and careful performance. Therefore, if treatment is necessary due to state regulations, strict surveillance, including measuring of antibiotic levels in blood, by experienced veterinary public health personnel is mandatory.

Plasma and tissue concentration and pharmacokinetics of chlortetracycline (CTC) was determined in milk-fed and conventionally fed Holstein calves. A two-compartment open model was used after a single intravenous dose (11 mg CTC/kg body weight). There were no significant differences between dietary treatments. The drug was rapidly distributed from plasma into the peripheral compartment but was slowly eliminated, with detectable concentration of CTC continuing for 72 h after dosing. A single-compartment model was used after a single oral dose (22 mg CTC/kg body weight). All but four of the kinetic parameters were significantly different for the two dietary treatments. Milk-fed calves had a larger area under the plasma level curve, a larger fraction of the dose absorbed, a smaller volume of distribution and a smaller overall body clearance rate. Estimated recovery of CTC in the urine of the milk-fed calves was greater, regardless of route of administration. The concentration of CTC in tissues following an oral dose was greatest in kidney, followed by liver, heart, skeletal muscle, spleen and brain. Tissue depletion of CTC closely paralleled the decline in plasma concentration.

An improved extraction procedure for the determination of oxytetracycline, tetracycline and chlortetracycline in urine, plasma and tissues by high-performance liquid chromatography is described. The addition of phenylbutazone (3,5-dioxo-1,2-diphenyl-4-n-butylpyrazolidine) to water, urine or plasma enhances the extraction of these compounds by ethyl acetate. The recovery of oxytetracycline from plasma is increased six fold and the need for two separate extractions of urine and plasma is eliminated. The formation of phenylbutazone-tetracycline ion pairs and their role in the extraction process is discussed.

Bacillus cereus was used as the assay organism for the quantification of chlortetracycline (CTC) in avian plasma. Antibiotic medium #8 gave significantly larger zones of inhibition than nutrient agar 1.5% when used as the assay medium (P less than or equal to 0.05). When the CTC concentration was measured in serum, citrated plasma, heparinized plasma, and oxalated plasma, no significant differences were found between the inhibition zone diameters produced on antibiotic medium #8. However, there was a significant decrease in the zone diameters produced on this medium when citrated whole blood, oxalated whole blood, and heparinized whole blood were used instead of plasma. The length of incubation of assay plates was inversely related to the inhibition zone diameter, with an incubation time of 8 hr giving the largest and most distinct zones. Storing prepared assay plates at 4 C for 24 hr before use appeared to decrease the variability of the inhibition zone diameters. Storage of citrated plasma at 4 C for 48 hr and at -60 C for 9 days resulted in no significant decreases in CTC concentrations.

A trial was conducted to determine the suitability of using a pelleted diet containing chlortetracycline (CTC) for treatment of chlamydiosis in macaws. Macaws, normally fed seed and fruit diets in captivity, are notoriously difficult to treat with CTC-medicated mash diets. Healthy macaws fed a pelleted diet containing 1% or 1.5% CTC for 30 or 45 days maintained adequate food intake and mean blood concentrations of 1-2 CTC micrograms/ml blood throughout the treatment period. There were no significant differences between blood concentrations induced by the different dietary CTC concentrations. Blood concentrations of 1 microgram/ml are considered therapeutic, so it is likely that 1% CTC-medicated pellets will be adequate for treating chlamydiosis in these species.

Male broiler chicks, when administered mixed organic acids via the drinking water for 3 days prior to water administration of chlortetracycline (CTC), showed no significant increases in the blood levels of the antibiotic. However, if the organic acids were administered simultaneously with the antibiotic, either via drinking water administration or via oral dosing, significant increases in the blood levels of the antibiotic were noted. With simultaneous administration of the antibiotic and mixed organic acids via the drinking water, a significant decrease in water intake was observed; however, in spite of the decrease in water intake and a concomitant decrease in CTC intake, significant increases in the blood levels of the CTC were still present. These data suggest that mixed organic acids, commonly used in the poultry industry, can be utilized to elicit an increase in CTC blood levels to a greater degree than would be anticipated without the use of the organic acids.

Parakeets were fed hulled millet seed containing 0.5% chlortetracycline (CTC) or minocycline. Blood concentrations of more than 1 micrograms CTC/ml and more than 5 micrograms minocycline/ml were obtained. Equivalent drug assay results were obtained from blood specimens collected by venipuncture or by use of treated filter-paper discs. The latter is a fairly simple method for assaying CTC concentrations in blood of treated psittacines.

Day-old broiler chicks were fed 0, 1.25, 2.5, and 5.0 micrograms aflatoxin/g of feed for 3 weeks. Chlortetracycline (CTC) was administered in the drinking water at a concentration of 50 mg/liter for 27 hr starting on Day 21. Three hours after initiation of the CTC treatment, birds receiving 2.5 and 5.0 micrograms/g dietary aflatoxin had significantly lower CTC in blood compared with the controls. At 12 and 27 hr after the initiation of CTC treatment, birds receiving any level of aflatoxin had significantly decreased blood levels of CTC compared with the controls. Intravenous injection of CTC of control birds and birds receiving 2.5 micrograms/g aflatoxin revealed a significant decrease in the elimination half-life of CTC and a significant increase in the total systemic clearance of CTC in the birds receiving dietary aflatoxin. Birds receiving 2.5 micrograms/g dietary aflatoxin also had a significant increase in the volume of gall bladder bile; however, this did not result in a greater amount of CTC being eliminated via bile. Studies on protein binding of CTC in the plasma of control birds and the plasma of birds receiving 2.5 micrograms/g dietary aflatoxin demonstrated that 60% more CTC is "free", or unbound, in the plasma of birds receiving no aflatoxin. These results suggest that aflatoxicosis lowers the plasma concentrations of CTC as a result of a decreased binding of CTC to plasma protein. This allows more unbound CTC to be available for elimination from the plasma by a means other than the liver, most likely via the kidney.