Pharmacokinetics and pleural reaction of doxycycline after intrapleural administration

: Tetracycline has been used for the local treatment of malignant pleurisy ever since of Robinson (1972) reported its effectiveness. In this report, we try to elucidate possible mechanisms of action of this drug from the viewpoints of (1) pharmacokinetic analysis following intrapleural administration, and (2) pleural reaction. The results were as follows: (1) In 5 patients with malignant pleural effusion, 500 mg of doxycycline was injected into the pleural cavity and pharmacokinetic analysis was performed. The clearance curve of doxycycline in pleural fluid was described by either a one-compartment model or a two-compartment model. The mean half life of slow space was 33.3 hr, which suggested delayed excretion of this drug from pleural space. (2) The direct effect of doxycycline on pleura was studied in rabbits. At a dose of 10 mg per kg of body weight, the mesothelial cells became cuboid and contained vacuoles in their cytoplasma. With increasing dose up to 40 mg per kg, the changes in mesothelial cells were enhanced. In submesothelial tissue, edema and cellular infiltration were noticed. Three weeks later, normalization of mesothelium was observed, being followed by connective tissue proliferation. These findings may support the efficacy of tetracycline for local treatment of malignant pleurisy.