Systemic detection of doxycycline after local administration

Abstract

Objectives. Controlled release delivery (CRD) systems are used to extend the half-life of topical antibiotics in gingival crevicular fluid (GCF), while avoiding systemic contamination with antibiotics. When multiple periodontitis sites are treated by subgingival application of a one-component copolymer gel containing 14% doxycycline, it is likely that low levels of the antibiotic can be detected in blood by high performance liquid chromatography (HPLC). Methods. Twelve patients with severe periodontitis and one single defect per patient were treated with one single subgingival application of a new one-component doxycycline gel (14%) in each defect (the UNISITE group). Furthermore, 12 patients with between 3 and 9 periodontal defects were treated with a single application of the same doxycycline gel in each defect, resulting in 3–9 applications per patient (the MULTISITE group). Doxycycline was separated and quantitatively measured with HPLC using a UV detector. Results. In saliva, the maximum doxycycline concentration of the MULTISITE patients was nearly 10-fold higher than in the UNISITE group. In GCF specimens, maximum doxycycline concentrations were the same magnitude in both the MULTISITE and UNISITE groups. Only one UNISITE patient showed detectable levels of doxycycline in blood serum (maximum application: 0.18 µg/ml). Six MULTISITE patients exhibited measurable concentrations of doxycycline in their serum samples (maximum values: 0.12–0.76 µg/ml). The mean systemic concentration following application of the doxycycline-containing gel to multiple sites was as high as 160 ng/ml within minutes following application. Within approximately 1 h, this fell to levels below the limit of detection by HPLC (<50 ng/ml). Conclusions. Systemic contamination with doxycycline after topical administration may occur even after unisite application if no periodontal dressing is used. Locally administered doxycycline can be identified in the systemic circulation at levels far below those expected to have antibacterial effects. Systemic concentration following application to a single site was always below levels capable of detection by HPLC.

• Antibiotics
• controlled release
• local delivery
• pharmacokinetics
• systemic contamination