Establishment of a research pharmacy to support Ebola clinical research in Liberia.

Objective: This article describes the establishment of a research pharmacy to support the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) vaccine study for Ebola virus disease.

Setting: This article describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia, in 2014 and 2015.

Practice Innovation: The need for the rapid establishment of infrastructure to support the Liberia-United States joint clinical research partnership in response to the emerging Ebola virus disease provided the opportunity for collaboration among Liberian and U.

Determination of desoxyepothilone B in nude mice plasma by liquid-liquid extraction and reversed-phase high-performance liquid chromatography.

A novel reversed-phase high-performance liquid chromatographic (HPLC) method has been established for the determination of a newly developed anti-cancer agent desoxyepothilone B (dEpo B) in nude mice plasma. The sample preparation involved deproteination of 200 microl of plasma sample first, followed by liquid-liquid extraction of the resultant supernatant with chloroform. The compound taxol was used as the internal standard.

Preclinical pharmacology of 2-methoxyantimycin A compounds as novel antitumor agents.

Purpose: The present study was designed to determine pharmacological and biochemical properties of 2-methoxyantimycin A analogs (OMe-A1, OMe-A2, OMe-A3, and OMe-A5), which are novel antitumor compounds, and provide a basis for future pharmaceutical development, preclinical evaluation, and clinical trials.

Methods: A high-performance liquid chromatography (HPLC) method was established and employed to assess the biostability of these analogs and to determine their pharmacokinetic properties in mice and rats.

Results: In vitro biostability of the 2-methoxyantimycin analogs was esterase-dependent, compound-dependent, and species-dependent.

Preclinical pharmacology of epothilone D, a novel tubulin-stabilizing antitumor agent.

Purpose: To determine, for various species, the pharmacological and biochemical properties of epothilone D (EpoD) that are relevant in establishing an appropriate animal model for further evaluation of this promising antitumor agent.

Methods: A method involving high-performance liquid chromatography (HPLC) was developed and used to assess the stability and protein binding of EpoD in plasma from various species, its metabolism by various S9 fractions, and its pharmacokinetics in mice.

Results: EpoD was stable in dog and human plasma.

Plasma and cellular pharmacology of 8-chloro-adenosine in mice and rats.

Purpose: The nucleoside 8-chloro-adenosine (8-Cl-Ado) is currently being developed for treatment of multiple myeloma and leukemias. Although accumulation of the phosphorylated drug product is known to occur within cell lines, its metabolic fate in plasma or circulating cells in animals is unclear. The purpose of the present study was to determine the pharmacology of 8-Cl-Ado in rodents through examination of plasma and cellular levels of parent drug and metabolites.

Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice.

Purpose: The purpose of the present study was to evaluate, in conjunction with the National Cancer Institute, the feasibility of using two thymidine analogs, 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU, NSC-678515) and 2'-fluoro-5-methyldeoxyuracil-beta-D-arabinofuranoside (FMAU, NSC-678516), as 18-fluorine-labeled positron emission tomography (PET) imaging agents.

Methods: The in vivo distribution and DNA incorporation of [2-(14)C]FAU, [2-(14)C]FMAU, and [2-(14)C]thymidine (as a control) were studied in SCID mice bearing human xenografts of T-cell leukemia CCRF-CEM. Levels of drug-associated radioactivity in blood, tumor and normal tissues including liver, kidneys, heart, lungs, spleen, brain, and skeletal muscle were determined.