Long-term pharmacokinetics of doxorubicin HCl stealth liposomes in patients after polychemotherapy with vinorelbine, cyclophosphamide and prednisone (CCVP)

Abstract

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.

Distribution of Doxorubicin in Rats Undergoing Ultrasonic Drug Delivery

“…A few of these applications include administration of free Dox (dissolved in saline) 23–25 , or loading the drug into carriers such as liposomes 23,24 or micelles. 26 Free Dox displays a biphasic deposition in plasma after intravenous injection in rats and humans.…”

Effect of small-sized liposomal Adriamycin administered by various routes on a metastatic breast cancer model

“…administration. Linkesch et al (2001) speculated that Caelyx remains stable in the blood for at least 14 days. Secondly, there is passive targeting of LADR to the mononuclear phagocyte system such as the liver, lungs, lymph nodes and marrow, the tissues most susceptible to the dissemination of breast cancer.…”

Unrelated SCT induces long-term remission in patients with blastic plasmacytoid dendritic cell neoplasm

“…for five consecutive days (total dose 500 mg) was applied (Hyper-CCVP). 10 One patient received a CHOP regimen combined with prophylactic intrathecal liposomal cytarabine and one hyper-CVAD as induction treatment. 11,12 Depending on each treatment regimen, up to six cycles were applied.…”