The primary goal of this study was to characterize the release profile of
doxycycline hyclate (8.5% w/w) from a biodegradable controlled-release delivery system (DH) placed in
periodontal pockets. Pharmacokinetic data were obtained from gingival crevicular fluid (GCF), saliva, and serum of
adult periodontitis patients. These results were compared to those obtained from individuals who received standard oral doses of
doxycycline hyclate (200 mg on day 0, then 100 mg/day for 7 days). All participants presented with multiple pockets > or = 5 mm that bled upon probing. At the baseline visit patients receiving local
drug delivery had all pockets > or = 5 mm that bled upon probing on one side of the mouth filled with DH.
Drug retention was enhanced with 1 of 2
periodontal dressings (non-
eugenol [NE] or 2-
octyl cyanoacrylate [2-octyl]).
Doxycycline concentrations were analyzed with the aid of reverse phase high performance liquid chromatography. GCF saliva, and serum samples were obtained just prior to
drug delivery and then at hours 2, 4, 6, 8, 18, 24 and days 2, 3, 5, 7, and 8. GCF and saliva samples were also obtained at days 10, 14, 21, and 28. Thirty two subjects participated in the study; 13 in the NE group, 13 in the 2-octyl group, and 6 in the group taking oral
doxycycline. The release of
doxycycline in the GCF peaked at 2 hours (1473 microg/ml in the NE group, and 1986 microg/ml in the 2-octyl group). The mean concentration at day 7 was 309 microg/ml for the NE group and 148 microg/ml for the 2-octyl group. Minimal levels of
drug were detected in the GCF of the oral
doxycycline group with a peak concentration of 2.53 microg/ml at 12 hours. Salivary concentrations for both local delivery groups peaked at hour 2 (4.05 microg/ml for the NE group and 8.78 microg/ml for the 2-octyl group); by the end of day 1 levels were < or = 2 microg/ml. For subjects who took the oral
doxycycline, salivary concentrations never exceeded 0.11 microg/ml. Serum concentrations of
doxycycline for individuals receiving the local
drug delivery never exceeded 0.1 microg/ml. For the oral
doxycycline group serum concentrations ranged from 0.91 to 2.26 microg/ml over the 8 days data were collected. The high concentration of
drug available at the treated sites coupled with the relatively low levels in the saliva and almost non-existent levels in the serum indicate that this biodegradable controlled-release delivery system displays an appropriate pharmacokinetic profile for the delivery of
doxycycline into
periodontal pockets.