Pharmacokinetics of etoposide after intrathoracic instillation to lung cancer patients with pleural effusion

Objective: To examine etoposide (VP16) levels in serum and pleural effusion after intravenous infusion or intrathoracic instillation to lung cancer pa tients. Methods: Four patients were administered VP16 by intrathoracic inst illation and three patients were administered it intravenously. Serum, urin e, and pleural effusion were collected and VP16 levels in the biological fl uids were determined by HPLC. Pharmacokinetic parameters were calculated. R esults: VP16 distributed rapidly into pleural effusion after intravenous in fusion. In two of three patients, VP16 levels in pleural effusion were main tained at constant levels more than 24 hours in spite of the decline in ser um VP16 levels. After intrathoracic instillation, VP16 in pleural effusion reached high levels and eliminated slowly. Serum levels of VP16 were relati vely low compared with those in pleural effusion. Conclusion: It was demons trated that intrathoracic instillation of VP16 might be useful for managing malignant pleural effusion and reducing systemic side-effects by cutting d own the dose.