Systemic drug administration(oral / IV / IM)

Drug enters systemic circulation(plasma – free drug fraction)

Gingival microcirculation(post-capillary venules of gingival plexus)

Vascular changes (in inflammation)• Vasodilation• Increased blood flow• Increased vascular permeability• Increased hydrostatic pressure

Plasma fluid + dissolved drug leakinto gingival interstitial space(Starling forces)

Gingival connective tissue drug pool(drug levels ≈ free plasma levels)

Uptake and storage in gingival cells• Fibroblasts• Epithelial cells• Immune cells (cellular reservoirs)

Slow efflux / release backinto interstitial fluid as blood levels fall

Movement toward gingival sulcuswith interstitial fluid

Passage through junctional epithelium• Few tight junctions• Highly permeable• Permeability ↑ in gingivitis/periodontitis

Drug-containing GCFin sulcus / periodontal pocket