[A pharmacokinetic study of teniposide in intraperitoneal chemotherapy of ovarian cancer].
The objectives of this study were to determine the characteristics of pharmacokinetics of teniposide (VM-26) instilled intraperitoneally with three dosages (100 mg, 150 mg and 200 mg) and to evaluate its toxicity. Twelve patients with ovarian cancer were divided into three groups: teniposide 100 mg i.p., 5 patients; teniposide 150 mg i.p., 5 patients; and teniposide 200 mg i.p., 2 patients. Samples of ascitic fluid, blood and urine were collected after administration of these drugs in 24 hours. Concentrations of teniposide were determined with high-performance liquid chromatographic procedure. The results showed that the data collected from peritoneum and plasma were found to conform to a two-compartment open model. The peak concentration (Cmax) and the area under the curves (AUC) in peritoneal cavity and plasma were dose-dependent. The ratios of Cmax and AUC between peritoneal fluid and plasma varied within 13.46 +/- 1.89 and 7.65 +/- 2.03 respectively. The elimination half-lives (T1/2 beta) in the peritoneum and plasma of teniposide were 5.28 +/- 0.95 and 6.64 +/- 2.73 hours respectively. The volume of peritoneal distribution and its clearance were lower than those of plasma (P < 0.001). The side effects were mild and were not dependent on drug dosage. The results suggest that teniposide as an intraperitoneal therapeutic agent offers some advantages in the treatment of ovarian cancer. The tumor tissues and peritoneal growths could be bathed in a high concentration of teniposide. Teniposide is safe, reasonable in intraperitoneal chemotherapy and shows prospects in the treatment of ovarian cancer.
Department of Obstetrics and Gynecology, Second Affiliated Hospital, WCUMS, Chengdu 610041.
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Cheng
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Peng
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Hong
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D011379:Prognosis; D013713:Teniposide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D013713:Teniposide