Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals.
Abstract: The objective of this study was to determine the disposition of orally administered doxycycline in foals. Six healthy 4- to 8-week-old foals were used. Doxycycline was administered to each foal via the intragastric (IG) route at dosages of 10 and 20 mg/kg, in a cross-over design. After the first 10 mg/kg dose, five additional doses were administered at 12-h intervals. A microbiological assay was used to measure doxycycline activity in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells. Following administration at 10 mg/kg, mean+/-SD time to peak serum doxycycline activity (tmax) was 3.0+/-1.2 h, maximum serum activity (Cmax) was 2.54+/-0.27 microg/mL, and terminal half-life (t1/2) was 8.5+/-2.8 h. Administration at a dose of 20 mg/kg resulted in a significantly longer tmax (5.5+/-1.8 h) as well as a tendency toward higher Cmax (2.89+/-0.33 microg/mL) and longer t1/2 (11.9+/-2.6 h). After multiple IG doses, doxycycline activity in CSF was significantly lower than concurrent serum activity, whereas peritoneal fluid, synovial fluid, and BAL cell doxycycline activity was similar to concurrent serum activity. Doxycycline activity in urine and PELF was significantly higher than that found at other sites. Oral administration at a dosage of 10 mg/kg every 12 h would maintain serum, PELF, and BAL cell activity above the minimum inhibitory concentrations of Rhodococcus equi, beta-hemolytic streptococci, and other susceptible bacterial pathogens for the entire dosing interval.
Publication Date: 2007-05-03 PubMed ID: 17472649DOI: 10.1111/j.1365-2885.2007.00857.xGoogle Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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This research investigates how the antibiotic doxycycline, administered orally, distributes within young foals. The research indicates that adjustment of dosage levels can maintain antibiotic levels above the required limit for combating certain bacterial infections in different body fluids and cells.
Study Design and Methodology
- The research was carried out on six healthy foals aged between 4 to 8-weeks.
- The antibiotic, doxycycline, was introduced to each foal intragastrically (directly into the stomach) at doses of 10 and 20 mg/kg.
- The 10 mg/kg dose was given continually at 12-hour intervals for five additional times while the 20 mg/kg dosage was given once.
- Post-administration, doxycycline activity was measured in serum, urine, peritoneal fluid, synovial fluid, cerebrospinal (CSF), pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells using a microbiological assay.
Results and Findings
- With a 10 mg/kg dosage, the peak serum doxycycline activity was seen at an average of 3.0 hours after administration, while the maximum serum activity was approximately 2.54 microgram/mL and the terminal half-life was 8.5 hours.
- The 20 mg/kg dose showed a longer peak serum doxycycline activity time (about 5.5 hours), a trend towards higher peak activity (about 2.89 microgram/mL), and a longer terminal half-life (11.9 hours).
- Continuous administration of doxycycline showed significantly lower activity in the CSF, compared to the simultaneous serum activity. On the other hand, the doxycycline activity in peritoneal fluid, synovial fluid, and BAL cells was similar to the concurrent serum activity.
- Doxycycline activity in urine and PELF was significantly higher than what was found in other areas of the body.
Conclusions
- The research suggests that oral administration of doxycycline at a dosage of 10 mg/kg every 12 hours would be sufficient to maintain serum, PELF, and BAL cell activity levels above the minimum inhibitory concentrations. This could effectively combat bacterial pathogens like Rhodococcus equi, beta-hemolytic streptococci, and other susceptible bacterial strains throughout the entire dosing interval.
Cite This Article
APA
Womble A, Giguère S, Lee EA.
(2007).
Pharmacokinetics of oral doxycycline and concentrations in body fluids and bronchoalveolar cells of foals.
J Vet Pharmacol Ther, 30(3), 187-193.
https://doi.org/10.1111/j.1365-2885.2007.00857.x Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
MeSH Terms
- Administration, Oral
- Animals
- Animals, Newborn / metabolism
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / urine
- Area Under Curve
- Ascitic Fluid / metabolism
- Bronchoalveolar Lavage Fluid / cytology
- Cerebrospinal Fluid / metabolism
- Cross-Over Studies
- Doxycycline / administration & dosage
- Doxycycline / blood
- Doxycycline / pharmacokinetics
- Doxycycline / urine
- Female
- Horses / metabolism
- Male
- Synovial Fluid / metabolism
Citations
This article has been cited 11 times.- Huang A, Mao F, Huang L, Xie S, Pan Y, Qu W, Cheng G, Liu Z, Yuan Z, Peng D, Hao H. PK-PD Modeling and Optimal Dosing Regimen of Acetylkitasamycin against Streptococcus suis in Piglets. Antibiotics (Basel) 2022 Feb 21;11(2).
- Drwiega EN, Rodvold KA. Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update. Clin Pharmacokinet 2022 Jan;61(1):17-46.
- Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA. Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi. J Clin Microbiol 2021 Sep 20;59(10):e0114921.
- Álvarez-Narváez S, Giguère S, Cohen N, Slovis N, Vázquez-Boland JA. Spread of Multidrug-Resistant Rhodococcus equi, United States. Emerg Infect Dis 2021 Feb;27(2):529-537.
- Lei Z, Liu Q, Yang B, Ahmed S, Cao J, He Q. The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis. Oncotarget 2018 Jan 5;9(2):1673-1690.
- Zhang P, Hao H, Li J, Ahmad I, Cheng G, Chen D, Tao Y, Huang L, Wang Y, Dai M, Liu Z, Yuan Z. The Epidemiologic and Pharmacodynamic Cutoff Values of Tilmicosin against Haemophilus parasuis. Front Microbiol 2016;7:385.
- Zozaya H, Gutierrez L, Bernad MJ, Sumano H. Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses. Acta Vet Scand 2013 Mar 8;55(1):21.
- Gutiérrez L, Velasco ZH, Vázquez C, Vargas D, Sumano H. Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs. Acta Vet Scand 2012 Jun 8;54(1):35.
- Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 2011 Oct;50(10):637-64.
- Huguet A-S, Gourbeyre O, Bousquet-Mélou A, Ferran AA, Lallemand EA. Reassessment of extracellular and intracellular activity of macrolides, rifampicin, and doxycycline against Rhodococcus equi based on bacterial counts and microscopy. Microbiol Spectr 2025 Sep 2;13(9):e0120525.
- Huguet AS, Gourbeyre O, Bernand A, Philibert C, Bousquet-Melou A, Lallemand EA, Ferran AA. Comparative bactericidal activity of four macrolides alone and combined with rifampicin or doxycycline against Rhodococcus equi at concentrations achievable in foals. Front Pharmacol 2024;15:1458496.
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