Trastuzumab and liposomal Doxorubicin in the treatment of mcf-7 xenograft tumor-bearing mice: combination does not affect drug serum levels.

Purpose: We assessed the combination of doxorubicin or liposomal doxorubicin with trastuzumab for alterations in peak serum drug levels, as these agents are increasingly being paired in the treatment of aggressive breast cancer. We hypothesized that trastuzumab would exhibit a slower rate of elimination from the serum when in combination with liposomal doxorubicin based on the known effects of liposomal doxorubicin on phagocytic cells of the mononuclear phagocyte system (MPS), which are responsible in part for the uptake and degradation of antibodies.

Methods: Doxorubicin and trastuzumab serum levels were assessed following injection of free doxorubicin, liposomal doxorubicin, or trastuzumab into female RAG2-M mice bearing subcutaneous MCF-7(HER-2) tumors.

An evaluation of transmembrane ion gradient-mediated encapsulation of topotecan within liposomes.

Topotecan can be encapsulated in liposomes, however little is known about the role encapsulated counter ions play in drug loading efficiency and drug release. Using 1,2-distearoyl-sn-glycero-3 phosphatidylcholine and cholesterol liposomes (55:45 mole ratio), encapsulation was achieved using manganese ion gradients (MnSO(4) or MnCl(2)), with the addition of A23187, a divalent cation/proton exchanger, to maintain a pH gradient. This methodology was compared to procedures where the pH gradient was generated by use of encapsulated (NH(4))(2)SO(4) or citrate (300 mM, pH 3.

Molecular and pharmacokinetic properties associated with the therapeutics of bcl-2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin.

Bcl-2 is a key apoptosis-regulating protein that has been implicated in mechanisms of chemoresistance for a variety of malignancies by blocking programmed cell death. This study investigated the activity of the Bcl-2 antisense oligodeoxynucleotide (AS ODN) G3139 combined with free doxorubicin (F-DOX) or sterically stabilized liposomal doxorubicin (SL-DOX) to determine the role that drug pharmacodistribution properties may have on antitumor activity using a Bcl-2-expressing human breast solid tumor xenograft model. Administration of G3139 was able to delay the growth of MDA435/LCC6 cells compared with control ODN-treated animals; however, in all of the cases, tumors reestablished after AS ODN treatment.

Phase I study of liposomal vincristine.

Purpose: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS).

Patients And Methods: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable.

Pharmacokinetic behavior of vincristine sulfate following administration of vincristine sulfate liposome injection.

The pharmacokinetic behavior of vincristine sulfate (VINC) following administration of vincristine sulfate liposome injection (VSLI), 0.16 mg/ml, as an intravenous infusion over 60 min in 24 of 25 patients enrolled in a phase I clinical study of this drug is described. Plasma samples for determination of the pharmacokinetic behavior of VINC were collected during the infusion at 15, 30 and 60 min as well as at 2, 4, 8, 12, 48 and 72 h postinfusion.

Validation of a high-performance liquid chromatographic assay method for quantification of total vincristine sulfate in human plasma following administration of vincristine sulfate liposome injection.

The validation of a high performance liquid chromatographic (HPLC) assay method for quantitation of total vincristine sulfate (VINC) in human plasma is described. VINC was extracted from plasma using BondElut CBA solid phase cartridges with vinblastine as the internal standard. Chromatography was accomplished using a Waters Symmetry C8 (250 mm x 4.

Chromatographic analysis and pharmacokinetics of liposome-encapsulated doxorubicin in non-small-cell lung cancer patients.

A sensitive and specific quantitative assay for total doxorubicin concentrations in plasma containing liposome-encapsulated doxorubicin hydrochloride (TLC D-99) was developed, with solvent extraction and reversed-phase high-performance liquid chromatography (HPLC). Separation of doxorubicin from its metabolites was accomplished with a 15 cm x 3.9 mm i.

Gas-chromatographic analysis of busulfan for therapeutic drug monitoring.

The development and validation of a gas chromatographic assay method for determination of total and free busulfan concentrations in human plasma for pharmacokinetic studies is reported. 1,6-Bis(methanesulfonyloxy)hexane, the internal standard, and a potential metabolite, 3-hydroxysulfolane, were synthesized. Plasma and plasma ultrafiltrate samples containing busulfan and internal standard were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination.