Pharmacokinetics of Pegylated Liposomal Doxorubicin

  title={Pharmacokinetics of Pegylated Liposomal Doxorubicin},
  author={Alberto A. Gabizon and Hilary Shmeeda and Yechezkel Barenholz},
  journal={Clinical Pharmacokinetics},
Pegylated liposomal doxorubicin (doxorubicin HCl liposome injection; Doxil® or Caelyx®) is a liposomal formulation of doxorubicin, reducing uptake by the reticulo-endothelial system due to the attachment of polyethylene glycol polymers to a lipid anchor and stably retaining drug as a result of liposomal entrapment via an ammonium sulfate chemical gradient. These features result in a pharmacokinetic profile characterised by an extended circulation time and a reduced volume of distribution… 
Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal Doxorubicin.
Pegylated liposomal doxorubicin has been approved for clinical use in a variety of neoplastic conditions because of its antitumor efficacy and unique safety profile with an impressive reduction of cardiac toxicity in comparison with conventional doxorbicin.
Comparison of Two Commercially Available Pegylated Liposomal Doxorubicin Products: Doxil/Caelyx versus Lipo-Dox
The current status of newly developed polyethyleneglycol-coated liposome (PEG-liposome or pegylated lyposome) is described in this review and it’s obvious that higher plasma AUC may not always be advantageous to patients who receive pegylation liposomal doxorubicin.
The hepatic pharmacokinetics of doxorubicin and liposomal doxorubicin.
Liposomal doxorubicin is restricted to the sinusoidal lumen, presumably secondary to steric exclusion by fenestrations in the Sinusoidal endothelium, which provides the mechanism for the longer half-life and reduced hepatic extraction of liposomalDoxorUBicin compared with doxorbicin.
Distinct biodistribution of doxorubicin and the altered dispositions mediated by different liposomal formulations.
A pegylated liposomal platform: pharmacokinetics, pharmacodynamics, and toxicity in mice using doxorubicin as a model drug.
It is demonstrated that the pegylated liposomes improve the efficacy of toxics and reduce the toxicity, therefore providing favorable evidence for building a Sino-pegylation liposomal platform.
Allometric scaling of pegylated liposomal anticancer drugs
Despite a strong correlation between body weight and MPS-associated variables with CL among preclinical species, the use of the equations did not predict CL and new methods of allometric scaling and measures of MPS function need to be developed.
Bioequivalence Study of Pegylated Doxorubicin Hydrochloride Liposome (PEGADRIA) and DOXIL ® in Ovarian Cancer Patients: Physicochemical Characterization and Pre-clinical studies.
Pegylated Doxorubicin Hydrochloride Liposome (PEGADRIA) was found to have similar physicochemical profile compared to Doxil® and was safe and bioequivalent to D Coxil® in ovarian cancer patients.
Direct comparison of two pegylated liposomal doxorubicin formulations: is AUC predictive for toxicity and efficacy?
Interaction of liposomes bearing a lipophilic doxorubicin prodrug with tumor cells
It is concluded that the most probable mechanism of the lipophilic prodrug penetration into a cell is liposome-mediated endosomal pathway.


Development of liposomal anthracyclines: from basics to clinical applications.
Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.
The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier.
Dose Dependency of Pharmacokinetics and Therapeutic Efficacy of Pegylated Liposomal Doxorubicin (DOXIL) in Murine Models
D dose escalation results in a saturation of Doxil clearance and a disproportional increase of the amount of liposomal drug accumulating in tumor, and a trend to superior therapeutic efficacy for treatments based on larger doses as compared to smaller split doses, while maintaining an equivalent dose intensity was observed.
Pharmacokinetics, Biodistribution and Therapeutic Efficacy of Doxorubicin Encapsulated in Stealth® Liposomes (Doxil®)
Doxil exhibits altered plasma pharmacokinetics, with a longer plasma half-life, large AUC and markedly smaller volume of distribution than Adriamycin and Tissue levels of doxorubicin are generally lo...
Preclinical Studies with Doxorubicin Encapsulated in Polyethyleneglycol-Coated Liposomes
The minimal lethal dose of DOX to tumor-free mice was substantially increased by encapsulation in PEG-coated liposomes, indicating that toxicity is reduced and the vesicant ofDOX after intradermal injection is prevented by liposome encapsulation.
Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial?
  • R. Hong, C. Huang, F. Chang
  • Chemistry, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
Although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the twoliposomal drug groups.
Sterically stabilized liposomes.
Tumour uptake of doxorubicin in polyethylene glycol-coated liposomes and therapeutic effect against a xenografted human pancreatic carcinoma.
This study tested the therapeutic efficacy of doxorubicin hydrochloride in two formulations: free in saline suspension and encapsulated in polyethylene glycol-coated, long-circulating liposomes, finding liposome-encapsulation was significantly more effective in inhibiting tumour growth and in effecting cures.
Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy.
The authors conclude that the use of long-circulating liposomes as cytotoxic drug carriers in brain tumor results in enhanced drug exposure and improved therapeutic activity, with equal effectiveness against early small- and large-sized brain tumors.