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

Citation
Nh. Stoller et al., THE PHARMACOKINETIC PROFILE OF A BIODEGRADABLE CONTROLLED-RELEASE DELIVERY SYSTEM CONTAINING DOXYCYCLINE COMPARED TO SYSTEMICALLY DELIVEREDDOXYCYCLINE IN GINGIVAL CREVICULAR FLUID, SALIVA, AND SERUM, Journal of periodontology, 69(10), 1998, pp. 1085-1091
Citations number
18
Categorie Soggetti
Dentistry,Oral Surgery & Medicine
Journal title
ISSN journal
00223492
Volume
69
Issue
10
Year of publication
1998
Pages
1085 - 1091
Database
ISI
SICI code
0022-3492(1998)69:10<1085:TPPOAB>2.0.ZU;2-I
Abstract
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.