Pharmacokinetic Profile of a Locally Administered Doxycycline Gel in Crevicular Fluid, Blood, and Saliva

Background: With the help of so‐called controlled release delivery systems, the half‐life period of locally administered antibiotics in gingival crevicular fluid (GCF) can be extended significantly. The aim of this study was to characterize the delivery profile of a new one‐component 14% doxycycline free amine gel for local application. Pharmacokinetics of doxycycline (DOXY) were analyzed in GCF, saliva, and serum. Methods: Twenty patients with persisting or recurring pockets (probing depths ≥5 mm and bleeding on probing) after mechanical treatment (surgical or non‐surgical) took part in the study. In each patient 1 periodontal defect was treated with DOXY gel. Samples of GCF, saliva, and serum were obtained before application of DOXY gel; 15 minutes after application; at 2 and 5 hours; and at 1, 2, 3, 4, 7, 9, and 11 days after application. Separation and quantitative measurement of DOXY was performed with high performance liquid chromatography and UV detection at λ = 260 nm. Results: Coefficients of variation were lower than 2% (intraassay) and 4% (interassay), respectively. For concentrations between 50 to 1000 μg/ml, we found a linear relationship between expected and measured DOXY values (linear coefficient of correlation: r = 0.998). Within the first 5 hours after application, concentration of DOXY in GCF (maximum after 15 minutes 19.97 ± 5.85 mg/ml) and saliva (maximum after 15 minutes 17.83 ± 2.84 mg/ml) was similar. Then concentration fell to a lower level (28.90 ± 19.44 μg/ml) compared to GCF (577.41 ± 127.34 μg/ml) after 3 days. Up to 10 days after application, the concentration of DOXY in GCF was 34.24 μg/ml. With the exception of 1 patient, all serum samples were DOXY‐negative. Conclusions: 1) After subgingival application of biodegradable 14% doxycycline gel, mean doxycycline levels in GCF that exceeded 16 μg/ml could be maintained for at least 12 days. Thus, the antimicrobial agent may be classified as a controlled release device. 2) The antibiotic effect was limited mainly to the subgingival sites of application of the doxycycline gel. 3) The doxycycline gel possesses the pharmacokinetic and clinical properties to deliver efficacious levels of antibiotics to the periodontal pocket and to maintain these levels for at least 1 week without the need of further drug retention by a periodontal dressing. J Periodontol 2002;73:1285‐1291.