Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma

• Published in: Cancer chemotherapy and pharmacology Vol. 15; no. 2; p. 149
• Main Authors: Canal, P, Bugat, R, Michel, C, Roche, H, Soula, G, Combes, P F
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1985
• Subjects: Aged; Ascitic Fluid - metabolism; Carcinoma - metabolism; Chromatography, High Pressure Liquid - methods; Electrochemistry; Female; Humans; Kinetics; Mathematics; Metabolic Clearance Rate; Ovarian Neoplasms - metabolism; Podophyllotoxin - analogs & derivatives; Proteins - analysis; Teniposide - blood; Teniposide - metabolism
• ISSN: 0344-5704
• DOI: 10.1007/BF00257526

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.