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Full-Text Articles in Medicine and Health Sciences
Evaluation Of The Pharmacokinetic-Pharmacodynamic Relationship, Metabolism And Plasma Protein Binding Of The Novel Antitumor Agent, 2-Methoxyestradiol (2me2), Following Oral Administration In Patients With Solid Tumors., Nehal Jagdish Lakhani
Theses and Dissertations
The goal of this study was to determine safety, tolerability and pharmacokinetics of 2ME2 in patients with solid tumors and determine maximum tolerated dose (MTD). The following hypotheses were tested: 1) 2ME2 will be well tolerated in clinic when given orally and will have quantifiable effects on the ex vivo markers of angiogenesis and apoptosis; 2) 2ME2 will exhibit linear pharmacokinetics; 3) Plasma protein binding will be extensive and linear; 4) Sulfation will be the major metabolic pathway for 2ME2.This was a phase I dose escalation study. Twenty patients with refractory solid tumors were enrolled. 2ME2 was administered orally starting …
Clinical Pharmacology Of Ms-275, A Histone Deacetylase Inhibitor, Milin R. Acharya
Clinical Pharmacology Of Ms-275, A Histone Deacetylase Inhibitor, Milin R. Acharya
Theses and Dissertations
The goal of this escalating single-dose phase I research study was to determine the safety, tolerability, pharmacokinetics, pharmacodynamics as well as in vitro metabolism and plasma protein binding of MS-275, a novel histone deacetylase inhibitor, in patients with solid tumors and lymphomas. A validated LC/MS assay was developed to quantitate MS-275 in plasma, human liver microsomes and urine. The pharmacokinetic (PK) evaluation was done using a non-compartmental approach. In-vitro plasma protein binding profile of MS-275 was characterized by a validated micro-equilibrium dialysis method. In vitro phase I and phase II hepatic metabolism of MS-275 were evaluated using human liver microsomes. …