Periodontal disease involves multiple interactions between bacterial biofilms and inflammatory responses of the periodontal connective tissue. Several MMPs play important roles in periodontal tissue breakdown by initiating extracellular matrix degradation.1 Tetracyclines can have therapeutic value by improving periodontal status through inhibition of MMP activity, independent of any antimicrobial properties.2 For this reason, SDDs have been intensively investigated for the treatment of chronic periodontitis in human medicine.3–6 The targeted plasma concentration for an SDD is recommended to be < 1 μg/mL, which is the MIC in humans.7
In canine dentistry, topical administration of doxycycline can resolve periodontal inflammation and improve periodontal status.8,9 A commercial topical doxycycline preparation in the form of a polymer can bind to the tooth surface. The subsequent slow release of doxycycline from the polymer matrix exerts a therapeutic effect consisting of antibiosis and local inhibition of collagenase activity.2,9 However, to date, no reports exist of an appropriate SDD for oral treatment of periodontitis in dogs. The inhibitory effect of long-term SDD treatment on MMP activity in periodontal tissue has not been determined in dogs to the authors’ knowledge.
Several analytic methods have been developed for the measurement of serum concentrations of antimicrobials in various species of animals.10–15 High-performance liquid chromatography is rapid, simple, and sufficiently sensitive to determine this concentration in microsamples of serum and has been successfully used in experimental studies.13,15 The purpose of the study reported here was to identify the optimal SDD of doxycycline for treatment of periodontitis in dogs. The desired dosing regimen would not result in a serum doxycycline concentration that exceeded the MIC but would result in clinical improvement through a hypothesized inhibitory effect on MMP activity in inflamed periodontal tissues.
DongKoo Pharm Co Ltd, Seoul, Republic of Korea.
SST Tube, BD, Franklin Lakes, NJ.
Mallinckrodt Baker Inc, Phillipsburg, NJ.
Yakuri Pure Chemicals Co Ltd, Osaka, Japan.
Waters Co, Milford, Mass.
Series 200 LC, PerkinEhlmer Inc, Shelton, Conn.
TotalChrom Workstation, version 6.3.1, PerkinElmer Inc, Shelton, Conn.
Alltima C18 5 μm, Grace Davison Discovery Science, Deerfield, Ill.
XP23-W Williams Explorer-Probe, Osung, Gimpo, Korea.
Tissue Extraction Reagent I, Invitrogen, Camarillo, Calif.
Protease Inhibitor Cocktail III, GenDEPOT, Barke, Tex.
Novex Tris-Glycine SDS Sample Buffer, Invitrogen, Carlsbad, Calif.
Novex Zymogram Renaturating Buffer, Invitrogen, Carlsbad, Calif.
Novex Zymogram Developing Buffer, Invitrogen, Carlsbad, Calif.
Amresco, Solon, Ohio.
Xpert Prestained Protein Marker, GenDEPOT, Barke, Tex.
Multi-gauge, version.3.0, Fujifilm, Tokyo, Japan.
LAS-3000, Fujifilm, Tokyo, Japan.
PASW Statistics, version 18, SPSS Inc, Chicago, Ill.
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