Medicine and Health Sciences Commons^™

Green Engineering And Gate-To Gate Life Cycle Assessments For Pharmaceutical Products, Daniel Fichana

Theses and Dissertations

The research of this thesis focused on the environmental and processing metrics during the development of two different drugs. Previous research in life cycle assessments and green engineering have focused on other products and processes, but only a limited amount of studies have been conducted for pharmaceutical applications. This analysis concerned a gate-to-gate analysis of two distinct pharmaceutical products along with the development of a solvent selection table. The goal of this research was to determine how various processing and environmental metrics were affected by process improvements.

The first drug was the pravastatin, which was made via a fermentation route. …

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. …

The Influence Of Direct-To-Consumer Advertising: Who Will Talk To Their Doctor As A Result Of Prescription Drug Advertisement?, Hai Dubo Chen

Theses and Dissertations

OBJECTIVES: To identify the types of patients who talk with their physicians as a result of Direct-to-Consumer (DTC) advertising. METHODS: Data were taken from a national survey, "Public Health Impact of Direct-to-Consumer Advertising of Prescription Drugs, July 2001- January 2002", conducted by researchers from Harvard Medical School. Participants (n = 3000) were interviewed by telephone. We constructed a conceptual framework consisting of outcomes (3 types of physician visits), intervention (DTC experience) and five groups of explanatory factors (health beliefs, demographics, health status, socioeconomic status and market factors). Data were analyzed with three multivariate stepwise logistic regressions. The three dependent variables …

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 …

A Nomogram For Valproic Acid And The Effect Of Missed Doses, Alaa M. Ahmad

Theses and Dissertations

Background. Clinicians are divided on dosing recommendations when a dose is delayed or missed. For a neuropsychiatric agent like valproic acid (VPA), rational dosing recommendations are of particular importance. VPA is subject to therapeutic monitoring using total concentrations. Due to non-linear binding of VPA to plasma proteins, current dose titration schemes for VPA are empirical. The objectives of this research were to 1- study the effect of missed/delayed doses on steady state concentrations of VPA and 2-design a nomogram that can be used for dose titration based on total VPA concentrations. Methods. 1- A simulation study was conducted to test …