Plasma pharmacokinetics of oral chlortetracycline in group fed, ruminating, Holstein steers in a feedlot setting

Reinbold, James B.; Coetzee, Johann F.; Gehring, Ronette; Havel, James A.; Hollis, Larry C.; Olson, K. C.; Apley, Michael D.

doi:10.1111/j.1365-2885.2009.1116.x

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…Concentrations of CTC in plasma were analyzed by high‐performance liquid chromatography as previously described (Reinbold et al ., ). More specifically, plasma samples, plasma spikes, and plasma QC samples, 0.200 mL, were treated with 1 m trichloroacetic acid (100 μL) after addition of the internal standard demeclocycline (10 μL of 10 ng/μL).…”

Section: Introductionmentioning

confidence: 97%

Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes

Washburn

Fajt

Plummer

et al. 2014

Vet Pharm & Therapeutics

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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.

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Section: Introductionmentioning

confidence: 97%

Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes

Washburn

Fajt

Plummer

et al. 2014

Vet Pharm & Therapeutics

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“…This consisted of a single 20-mg/kg of body weight intramuscular injection of oxytetracycline (Tetradure 300; Merial Limited, Duluth, GA, USA) followed 3 days later by 30 days of 8.8 mg/kg of body weight of granular chlortetracycline calcium complex (Aureomycin 50 Granular; Alpharma, Inc.) given once per day in the feed. Sera were collected from animals 3 days before oral treatment and at 14 and 35 days after the beginning of treatment, and were assayed for the presence of chlortetracycline by the Veterinary Diagnostic Laboratory at Iowa State University (27). Oral administration of chlortetracycline resulted in a mean serum concentration of 298 ng/ml on day 14, halfway through the treatment period.…”

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confidence: 99%

Immunization-Induced Anaplasma marginale-Specific T-Lymphocyte Responses Impaired by A. marginale Infection Are Restored after Eliminating Infection with Tetracycline

Turse

Scoles

Deringer

et al. 2014

Clin. Vaccine Immunol.

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bInfection of cattle with Anaplasma marginale fails to prime sustained effector/memory T-cell responses, and high bacterial load may induce antigen-specific CD4 T exhaustion and deletion. We tested the hypothesis that clearance of persistent infection restores the exhausted T-cell response. We show that infection-induced T-cell exhaustion, characterized as loss of antigen-specific proliferation, and gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) production are partially restored in cattle following clearance of persistent infection with tetracycline. For a little over a decade, it has been appreciated that certain chronic infectious diseases and cancers result in a loss of T-cell function that has been termed T-cell exhaustion (reviewed in references 1-5). T-cell exhaustion is a progressive loss of effector T-cell functions, beginning with production of interleukin 2 (IL-2), followed by tumor necrosis factor alpha (TNF-␣), then gamma interferon (IFN-␥), and eventually leading to T-cell death (2). This has been shown to occur for both CD8 and CD4 T cells (5, 6), but the most widely studied examples show a loss of effector CD8 T-cell function during chronic viral infections characterized by a relatively high antigen load (2,3,4,7,8,9). Furthermore, in a noninfection mouse model where CD4 T cells were exposed to persistent antigen (moth cytochrome c), a dose-and time-dependent persistence of antigen beyond the T-cell expansion phase resulted in a dysfunctional memory response. Following removal of the antigen, the T cells regained proliferative capacity (10).Evasion of innate and adaptive immune responses occurs with many pathogenic bacteria that establish chronic infection (11-13). Anaplasma marginale is a tick-borne intraerythrocytic rickettsial pathogen that causes acute bacteremia and anemia, which resolves into a lifelong persistent infection in the ruminant host (14). One well-described strategy of immune escape shared by pathogenic bacteria is antigenic variation (15). During A. marginale infection, variation in the major surface protein 2 (MSP2) enables the bacteria to escape a variant-specific antibody response (16). However, antigenic variation in MSP2 is not sufficient to explain the inability to clear infection. When cattle were immunized with native MSP2 comprised of a complement of variant MSP2s and infected with bacteria expressing the same major MSP2 variants, there was no protection against infection with bacteria expressing these MSP2 variants (17). This occurred even though immunization with native MSP2 induced CD4 proliferative and IFN-␥-secreting T-cell and IgG responses specific for the major MSP2 variant (18).To further explore the failure of MSP2 to protect against infection in the face of variant-specific immune responses, T-cell responses were monitored throughout the course of infection in the MSP2 vaccinees, and it was discovered that near the peak of bacteremia during acute infection, T-cell responses specific for A. marginale, but not other vaccine antigens, were lost...

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“…Reinbold et al [25] also gathered blood samples more frequently (sometimes as often as every 4 h) than the present study, likely contributing to differences in plasma CTC concentrations. However, at no time during the present study did more than 16.2 h, the oral CTC elimination half-life established for cattle [37], elapse between CTC feeding and blood sampling. Higher drug concentrations, achieved by CTC administration at levels higher than approved, may have contributed to greater bacteriostasis and subsequent Am clearance.…”

Section: Discussionmentioning

confidence: 56%

Failure to Eliminate Persistent Anaplasma marginale Infection from Cattle Using Labeled Doses of Chlortetracycline and Oxytetracycline Antimicrobials

Curtis

Anantatat

Martin

et al. 2021

Veterinary Sciences

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Bovine anaplasmosis, caused by the intracellular rickettsial pathogen Anaplasma marginale, is the most prevalent tick-transmitted disease of cattle worldwide. In the U.S., tetracycline antimicrobials are commonly used to treat and control anaplasmosis. Oxytetracycline, administered by injection, is indicated for treatment of clinical anaplasmosis in beef and dairy cattle and calves. Chlortetracycline, administered orally, is indicated for control of active anaplasmosis infection in beef and nonlactating dairy cattle. Tetracyclines have been demonstrated to be effective for treating active anaplasmosis, but their ability to eliminate A. marginale at currently approved therapeutic doses or dosing regimens remains unclear. In the absence of approved dosing regimens for A. marginale clearance, a study was conducted to determine the effect of approved oxytetracycline and chlortetracycline indications on A. marginale bacteremia. Fifteen animals with persistent anaplasmosis were enrolled and divided into three treatment groups. Group 1 (n = 6) received oral chlortetracycline (1.1 mg/kg bodyweight) administered via hand-fed medicated feed for 60 consecutive days. Group 2 (n = 6) received injectable oxytetracycline administered subcutaneously at 19.8 mg/kg bodyweight three times in 3-week intervals. Group 3 (n = 3) served as an untreated control. After 60 days, bacteremia failed to permanently decrease in response to treatment. This result indicates that clearance of A. marginale is unlikely to be reliably achieved using currently approved tetracycline-based regimens to manage anaplasmosis.

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Plasma pharmacokinetics of oral chlortetracycline in group fed, ruminating, Holstein steers in a feedlot setting

Cited by 12 publications

References 14 publications

Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes

Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes

Immunization-Induced Anaplasma marginale-Specific T-Lymphocyte Responses Impaired by A. marginale Infection Are Restored after Eliminating Infection with Tetracycline

Failure to Eliminate Persistent Anaplasma marginale Infection from Cattle Using Labeled Doses of Chlortetracycline and Oxytetracycline Antimicrobials

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