title: Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma.
abstract: Nine patients with ovarian carcinoma and malignant ascites treated with IV teniposide chemotherapy (30 mg/m2/30 min) entered this study. Plasma and peritoneal fluid levels were measured by an HPLC method with electrochemical detection. Plasma decay kinetics followed a triexponential function. A high variability of drug diffusion in ascites was noticed. Peak concentrations in ascites ranged from 1.6% to 20.5% of serum peak concentration. The concentration in peritoneal fluid reached a maximum level 6 h after the infusion ended. Teniposide was less slowly eliminated from ascites than from serum. The exposure of the inflammatory peritoneal fluid to the drug expressed by area under the concentration-time curve (AUC) was also subject to significant interindividual variation, ranging from 223 to 2332 micrograms/ml X min. However, the peritoneal AUC was correlated with serum AUC and with the systemic clearance of the drug. A significant relationship between gamma glutamyltranspeptidase and both systemic clearance and either the serum or the peritoneal AUC was found, suggesting that liver plays a role in drug disposition.
mesh_terms: D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004563:Electrochemistry; D005260:Female; D006801:Humans; D007700:Kinetics; D008433:Mathematics; D008657:Metabolic Clearance Rate; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D011506:Proteins / Q000032:analysis; D013713:Teniposide / Q000097:blood / Q000378:metabolism*
chemical_list: D011506:Proteins; D013713:Teniposide; D011034:Podophyllotoxin