THE PHARMACOKINETIC PROFILE OF A BIODEGRADABLE CONTROLLED-RELEASE DELIVERY SYSTEM CONTAINING DOXYCYCLINE COMPARED TO SYSTEMICALLY DELIVEREDDOXYCYCLINE IN GINGIVAL CREVICULAR FLUID, SALIVA, AND SERUM

THE PRIMARY GOAL OF THIS STUDY was to characterize the release profile of doxycycline hyclate (8.5% w/w) from a biodegradable controlled-rel ease delivery system (DH) placed in periodontal pockets. Pharmacokinet ic data were obtained from gingival crevicular fluid (GCF), saliva, an d serum of adult periodontitis patients. These results were compared t o 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 greater than or equal to 5 mm that bled upon probing. At the baseline visit patients receiving local drug delivery had all pockets greater than or equal to 5 mm tha t bled upon probing on one side of the mouth filled with DH. Drug rete ntion 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 chromat ography. GCE saliva, and serum samples were obtained just prior to dru g delivery and then at hours 2, 4, 6, 8, 18, 24 and days 2, 3, 5, 7, a nd 8. GCF and saliva samples were also obtained at days 10, 14, 21, an d 28. Thirty two subjects participated in the study; 13 in the NE grou p, 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 mu g/m l in the NE group, and 1986 mu g/ml in the 2-octyl group). The mean co ncentration at day 7 was 309 mu g/ml for the NE group and 148 mu g/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 mu g/ ml at 12 hours. Salivary concentrations for both local delivery groups peaked at hour 2 (4.05 mu g/ml for the NE group and 8.78 mu g/ml for the 2-octyl group); by the end of day 1 levels were less than or equal to 2 mu g/ml. For subjects who took the oral doxycycline, salivary co ncentrations never exceeded 0.11 mu g/ml. Serum concentrations of doxy cycline for individuals receiving the local drug delivery never exceed ed 0.1 mu g/ml. For the oral doxycycline group serum concentrations ra nged from 0.91 to 2.26 mu g/ml over the 8 days data were collected. Th e high concentration of drug available at the treated sites coupled wi th the relatively low levels in the saliva and almost non-existent lev els in the serum indicate that this biodegradable controlled-release d elivery system displays an appropriate pharmacokinetic profile for the delivery of doxycycline into periodontal pockets.