Purpose: Significant variability in the pharmacokinetics and pharmacodynamics of PEGylated liposomal doxorubicin (PLD) exists. PLD undergoes clearance via the mononuclear phagocyte system (MPS). Technetium Tc 99m sulfur colloid (TSC) is approved for imaging MPS cells.
View Article and Find Full Text PDFIntroduction: Studies have shown that body composition, age, gender, changes in monocyte count and repeated dosing alter pharmacokinetic properties of PEGylated liposomal doxorubicin (PLD). However, limited information exists regarding the clinical risk factors of ovarian cancer patients who develop palmar plantar erythrodysesthesia (PPE) while receiving PLD for cancer recurrence.
Methods: We conducted a retrospective cohort analysis of consecutive patients with recurrent ovarian and primary peritoneal cancer who were treated with PLD from 2005 to 2009.
As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose.
View Article and Find Full Text PDFUnlabelled: A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Inter-patient PK variability of 9 liposomal and SM formulations of the same drug was evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range).
View Article and Find Full Text PDFPurpose: Nanoparticles or carrier-mediated agents have been designed to prolong drug circulation time, increase tumor delivery, and improve therapeutic index compared to their small-molecule counterparts. The starting dose for phase I studies of small molecules and nanoparticles anticancer agents is based on the toxicity profile of the most sensitive species (e.g.
View Article and Find Full Text PDFJ Pharmacokinet Pharmacodyn
October 2011
Pegylated liposomal formulations contain lipid conjugated to polyethylene glycol. The disposition of encapsulated drug is dictated by the composition of the liposome, thus altering the pharmacokinetic (PK) profile of the drug. Allometric scaling is based on a power-log relationship between body weight (W) and drug clearance (CL) among mammals and has been used to compare the disposition of nonliposomal drugs across species.
View Article and Find Full Text PDFInfect Drug Resist
July 2011
Antibiotics offer great benefits by reducing the duration and severity of illnesses and aiding in infection transmission control. With this being said, the inexorable process of antimicrobial drug resistance is to some degree unavoidable. Although drug resistance will likely persist and is to be expected, the overall level can be dramatically decreased with increased attention to antibiotic overuse and the pharmacokinetic and pharmacodynamic properties of different drug formulations, and the use of proper hygiene and protective barriers.
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