Doxorubicin levels in the serum and ascites of patients with ovarian cancer.
OBJECTIVE
To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs.


METHODS
The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin.


RESULTS
Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum.


CONCLUSIONS
Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.
Gotlieb
W H
WH
Division of Gynecologic Oncology, Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, Suite A-632, Montreal, QC H3T 1E2, Canada. walter.gotlieb@mcgill.ca
Bruchim
I
I
Ben-Baruch
G
G
Davidson
B
B
Zeltser
A
A
Andersen
A
A
Olsen
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D001201:Ascites / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009279:Naphthacenes / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019152:Paracentesis; D011379:Prognosis
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C074869:7-deoxy-13-dihydroadriamycinone; D004317:Doxorubicin; C010013:adriamycinol; C049326:7-deoxyadriamycin aglycone