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Experimental determination of a subantimicrobial dosage of doxycycline hyclate for treatment of periodontitis in Beagles

Se Eun Kim DVM1, Soohee Kim DVM2, Manbok Jeong DVM, PhD3, Yesran Lee DVM4, Jeong Taek Ahn DVM5, Young Woo Park DVM6, Jae Sang Ahn DVM7, Euiri Lee DVM8, Doug-Young Ryu DVM, PhD9, and Kangmoon Seo DVM, PhD10
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  • 1 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 2 Laboratory of Environmental Health, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 3 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 4 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 5 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 6 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 7 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 8 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 9 Laboratory of Environmental Health, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
  • | 10 Department of Veterinary Surgery and Ophthalmology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.

Abstract

Objective—To identify a subantimicrobial dose of doxycycline hyclate (SDD) and for the treatment of periodontitis in dogs.

Animals—20 healthy Beagles for measurement of serum doxycycline concentration and 15 Beagles with periodontitis for evaluation of the efficacy of the SDD.

Procedures—5 dogs each received doxycycline hyclate PO at a dose of 1, 2, 3, or 5 mg/kg. Blood samples were collected before and after administration, and serum concentrations of doxycycline were measured via high-performance liquid chromatography. Mean serum doxycycline concentrations were calculated, and SDDs were identified. In a separate trial, the identified SDDs (1 or 2 mg/kg) were administered PO once a day for 1 month to dogs with periodontitis (n = 5/group) and a control group (5) was fed vehicle only during the same period. Degree of gingival attachment and bleeding on probing (present or absent) were recorded. Gingival samples were collected before and after the 1-month period from the same anatomic sites. Degree of matrix metalloproteinase inhibition in gingival samples was determined via gelatin zymography and compared among treatment groups.

Results—Mean serum doxycycline concentrations in healthy dogs that received 1 or 2 mg of doxycycline/kg were consistently significantly lower than the minimal inhibitory doxycycline concentration for treatment of periodontitis throughout the 24-hour posttreatment period. Zymographic intensities were lower in dogs given 1 and 2 mg/kg than in the control dogs, and the degree of gingival attachment and bleeding significantly improved in dogs given 2 mg/kg, compared with in the control dogs and dogs given 1 mg of doxycycline/kg.

Conclusions and Clinical Relevance—A doxycycline dosage of 2 mg/kg daily appeared to be an appropriate subantimicrobial regimen for dogs with periodontitis. Furthermore, this dosage may be suitable for long-term treatment of gelatinolytic inflammatory diseases such as periodontitis in this species.

Contributor Notes

Supported by the BK21 Program for Veterinary Science and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University.

Address correspondence to Dr. Seo (kmseo@snu.ac.kr).