title: Clinical pharmacokinetics of mitoxantrone after intraperitoneal administration.
abstract: The pharmacokinetics of intraperitoneally (i.p.) injected mitoxantrone was determined in plasma and peritoneal dialysate taken from five patients presenting with cancer confined to the peritoneal cavity over a sampling period of 1 week. The drug was given through a Tenckhoff catheter as a 15-min infusion and the peritoneal dialysate was removed after a dwell time of 4 h; the doses delivered varied between 20 and 50 mg/m2. Dose-limiting local toxicity was moderate. The HPLC technique used for mitoxantrone determinations proved to be sensitive within the range of 0.3-4,000 ng/ml. Median values obtained for the pharmacokinetic parameters of mitoxantrone in peritoneal dialysate were: t1/2 beta (distribution), 56.4 min (range, 16.8-235.8 min); t1/2 gamma (elimination), 128 h (range, 28.3-171.0 h); Vdss (volume of distribution at steady state), 24.8 l (range, 17.0-232.5 l); delta'ss (volume of distribution at steady state corrected for the body surface area in square meters), 14.4 l/m2 (range, 10.6-129.2 l/m2); and clearance, 0.25 l/h (range, 0.16-0.59 l/h). For plasma the median values were: t1/2 alpha (absorption), 58.8 min (range, 45.6-87.0 min); t1/2 beta (distribution), 2.5 h (range, 1.4-6.3 h); t1/2 gamma (elimination), 44.1 h (range, 9.1-91 h); Vdss, 2,152 l (range, 352-19,733 l); delta'ss, 1,345 l/m2 (range, 220-11,606 l/m2); and clearance, 117 l/h (range, 51-1,609 l/h). After 168 h the median plasma concentration was 1 ng/ml. The median peak concentration in peritoneal dialysate was 490 ng/ml. Considering the moderate toxicity observed and the concentrations achieved in the peritoneal dialysate, removal of the dialysate after certain dwell times seems reasonable to be a reasonable approach for the optimization of i.p. treatment with mitoxantrone.
authors.affiliation: University Clinic of Bonn, Department of Pediatric Oncology and Hematology, Federal Republic of Germany.
authors.forename: J D
authors.initials: JD
authors.lastname: Nagel
authors.forename: F J
authors.initials: FJ
authors.lastname: Varossieau
authors.forename: R
authors.initials: R
authors.lastname: Dubbelman
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: J G
authors.initials: JG
authors.lastname: McVie
mesh_terms: D000008:Abdominal Neoplasms / Q000378:metabolism / Q000473:pathology; D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D008942:Mitoxantrone / Q000493:pharmacokinetics* / Q000633:toxicity; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary
chemical_list: D008942:Mitoxantrone