Comparison of the pharmacokinetic profiles of two locally administered doxycycline gels in crevicular fluid and saliva

J Clin Periodontol. 2004 Apr;31(4):286-92. doi: 10.1111/j.0303-6979.2004.00494.x.


Background: Controlled-release delivery systems enable the clinician to extend the half-life period of locally administered antibiotics in gingival crevicular fluid (GCF) significantly. The aim of this split-mouth study was to compare the pharmacokinetic profile of two different doxycycline gels (DOXY and ATRI) for topical subgingival application. Pharmacokinetics of both doxycycline gels were analyzed in GCF and saliva.

Methods: In 10 patients suffering from severe periodontitis, 10 pairs of contralateral defects (pocket depth > or =5 mm/bleeding on probing or > or =6 mm) were randomly assigned either to the first application of DOXY or ATRI. Fourteen days after the topical application of the first antibiotic gel, the application of the second gel in the contralateral defect took place. Clinical examinations at baseline showed no significant differences between sites treated with DOXY and ATRI. Samples of GCF and saliva were drawn baseline, 2, 5 and 24 h after application, 2, 3, 4, 7, 9 and 11 days after application. Separation and quantitative measurement of both doxycycline-gels was performed with HPLC- and UV-detection at lambda=260 nm.

Results: In saliva specimens, time-dependent changes of mean doxycycline concentration were almost identical for both doxycycline-gels and declined from a maximum 2 h after application (ATRI: 6653.90+/-3096.14 microg/ml; DOXY: 5386.60+/-1542.02 microg/ml [arithmetic mean+/-SEM]) to zero values 9 days after application. In crevicular fluid specimens, sites treated with ATRI exhibited a faster decrease of mean doxycycline concentration (1085.30, 264.00, 273.94, and 258.00 microg/ml measured 2, 5, 24, and 48 h after application) than sites treated with DOXY (1388.38, 1300.40, 803.73, and 235.10 microg/ml). The faster decrease of ATRI compared with DOXY could not be proved to be statistically significantly different.

Conclusions: Both doxycycline gels showed pharmacokinetics of controlled-release delivery systems.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Delayed-Action Preparations
  • Doxycycline / administration & dosage
  • Doxycycline / analogs & derivatives*
  • Doxycycline / pharmacokinetics*
  • Female
  • Follow-Up Studies
  • Gels
  • Gingival Crevicular Fluid / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Periodontitis / drug therapy
  • Saliva / metabolism*
  • Spectrophotometry, Ultraviolet


  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Gels
  • Doxycycline