Long-term pharmacokinetics of doxorubicin HCl stealth liposomes in patients after polychemotherapy with vinorelbine, cyclophosphamide and prednisone (CCVP).
The concentration-time profiles of Doxorubicin (DOXO) from day 0 to day 21 after i.v. infusion of 25 or 30 mg/m2 doxorubicin HCI stealth liposomes (Caelyx) were investigated in 9 patients receiving combination polychemotherapy with cyclophosphamide, vinorelbine and prednisone. Peak serum concentrations occurred from 0.04 to 4.0 days after infusion (mean tmax = 1.79 +/- 1.55 d) with a mean cmax of 4,595 +/- 2,849 ng/ml. A total amount of 12.84 +/- 2.47 mg liposomal DOXO in the plasma volume (Vp = 2,794 + 537 ml) could be estimated at tmax (= 27 % of the mean dose of 47.6 mg). Stealth liposomes were eliminated slowly from the blood with a mean t 1/2el of 1.9 + 0.5 days (MRT was 4.6 + 2.5 days). AUClast values ranged from 8,070 to 33,446 ng/ml*d (mean 10,987 +/- 9,339 ng/ml*d). The low plasma clearance (Cltot = 4,681 +/- 2,835 ml/day) and the small volume of distribution (Vz = 11.7 +/- 6.31) suggested that stealth-liposomes were stable in the blood at least for 14 days. Polychemotherapy with Hyper-CCVP schedule did not alter the stability of stealth liposomes, but peak levels of DOXO seemed to be somewhat lower compared to regression analysis of literature data (cmax versus dosage range from 20 to 60 mg/m2). Due to clast occurring between day 12 to 18, no indices for an accumulation of the drug in the blood could be found, when liposomes were given every four weeks.
Linkesch
W
W
Dep of Medicine, University Clinic of Graz, Austria.
Weger
M
M
Eder
I
I
Auner
H W
HW
Pernegg
C
C
Kraule
C
C
Czejka
M J
MJ
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D019540:Area Under Curve; D002945:Cisplatin / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D017567:Karnofsky Performance Status; D008081:Liposomes; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin