[Effective levels of cyclophosphamide and metabolites in pleural effusions during intravenous therapy (author's transl)].
Levels of cyclophosphamide (CP, Endoxan) and metabolites were determined in blood and pleural effusions of 5 cancer patients receiving 20 mg/kg CP i.v. The pleural concentrations of CP and its stable deactivated metabolites as 4-keto-CP and carboxyphosphamide increased slowly and even after 4 to 6 an equilibrium with plasma levels was not achieved completely. Plasma peak levels of activated CP (4-hydroxy-CP + aldophosphamide) determined after conversion into the stable derivative 4-(S-benzyl)sulfido-CP or by a fluorometric test were in the range of 1 to 2 nmol/ml. Using these techniques, as two independent methods, amounts of activated CP in pleural effusion were found to be below the limit of detection (0.1-0.2 nmol/ml). Also the alkylating rates of proteins in the pleural effusions were only 20% of those measured in blood samples. The relatively short plasma half-life (approx. 15 min) of 4-hydroxy-CP, when compared with the slow passage of CP-metabolites from blood to the pleural space, is assumed to be the reason for the failure of detection of activated CP and low levels of alkylating material observed in the pleural effusions.
D001711:Biotransformation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D010996:Pleural Effusion / Q000378:metabolism*; D011485:Protein Binding
D003520:Cyclophosphamide
Wirkspiegel von Cyclophosphamid und Metaboliten in malignen Pleuraergüssen bein intravenöser Therapie.