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Claudette Bethune, Ph.D.

Pharmacokineticist

Dr. Bethune has a doctorate in Pharmaceutics from the University of Washington, Seattle, WA with expertise in pharmacokinetics and drug metabolism. From August 2003 to March 2006, Dr. Bethune worked as a senior scientist in the department of seafood safety for the Norwegian government at the National Institute of Nutrition and Seafood Research (NIFES). In May of 2006, Dr. Bethune returned to the United States to continue work as a pharmacokineticist.

Articles by Dr. Bethune

• Norwegian farmed salmon production raises global concern - May 31, 2006
  The quality of Norwegian farmed salmon has recently come into question with the Russian ban, illegal nitrate use, and a building body of evidence that consumers should limit their consumption.

Dr. Bethune's Curriculum Vitae

Education

Ph.D. Pharmaceutics - The University of Washington, Seattle, Washington, 1999

• Major: Pharmacokinetics

  This course of study included an advanced and comprehensive evaluation of absorption, distribution, metabolism, excretion (ADME), and pharmacodynamic modeling for classical small-molecule agents as well as large molecular therapeutics.

• Minor: Drug Metabolism

  These studies critically evaluated and characterized the principal enzymes responsible for drug metabolism.

• Thesis:

  The Role of Drug-Lipid Interactions in Altered Biodistribution and Therapeutic Effects for Drugs Incorporated into Liposomes

Bachelor of Science - The Evergreen State College, Olympia, Washington, 1992

• Major: Biology and Chemistry

Associates of Science - Kapiolani Community College, Honolulu, Hawaii, 1988

• Major: Medical Laboratory Technology

Research Interest

Discovering and optimizing therapeutic efficacy, or elucidating toxicity, for new and existing compounds through drug metabolism and pharmacokinetic/pharmacodynamic analyses.

Experience

August 2003-March 2006: Senior Scientist - National Institute of Nutrition and Seafood Research (NIFES), Norway Department of Seafood Safety

• Work primarily included human risk assessment from seafood contaminants, developing and optimizing analytical processes and methods for reporting contaminant levels in biological matrices, collaboration and review on the design, analysis, and interpretation of surveillance and pharmacokinetic/pharmacodynamic studies.
• Attended relevant conferences and publishing articles on significant findings in international peer-reviewed journals.
• Proficient on: GC/MS, LC/MS (single-quad, ion trap), and LC/MS/MS platforms. In vitro tissue culture and in vivo animal models. WinNonlin - Industry-Standard PK/PD Modeling and Analysis. Laboratory information management systems and GLP quality control

July 2001-July 2003: Research Scientist I - Pfizer Global Research & Development, La Jolla Laboratories, USA Pharmacokinetics, Dynamics and Metabolism Department

• Managed several discovery oncology projects, supervised several associates, and characterized with comprehensive in vitro and in vivo techniques numerous novel compounds for a variety of chemotherapeutic targets.
• In vitro experiments included protocol development and analytical methodology for metabolic stability; P450 enzyme inhibition, induction, and identification; protein binding; blood to plasma partitioning
• In vivo studies included oral and systemic delivery of novel agents to small and large animals to determine the pharmacokinetics for compound optimization and prediction of human clearance mechanisms and dosing regimens. Pharmacokinetic/Pharmacodynamic modeling with biomarkers in small animals.
• Proficient on: LC/MS (single-quad, ion trap), and LC/MS/MS platforms. WinNonlin, additional certificate training - Industry-Standard PK/PD Modeling and Analysis. In vitro tissue culture (induction, CaCo2) and in vivo animal models. Laboratory information management systems and GLP quality control measures.

October 1999-July 2001: Scientist - SkyePharma, Inc., San Diego, CA, USA Research and Development

• Performed research and development of proprietary lipid delivery-systems through formulation, stability, and pre-clinical pharmacokinetic/pharmacodynamic studies.
• Characterized the non-linear pharmacokinetics and consequent pharmacodynamic behavior of several sustained-release formulations of large molecular therapeutic agents.
• Participated in the creation of a pipeline for the selection of new drug candidates for existing delivery systems.
• Proficient on HPLC, in vitro tissue culture and in vivo animal tumor models, and WinNonlin - Industry-Standard PK/PD Modeling and Analysis. Laboratory information management systems and GLP quality control measures.

September 1993- October 1999: Research Assistant - The University of Washington, Seattle, WA Department of Pharmaceutics

• Formulated and characterized the association of the nitrosourea lomustine (CCNU) with small unilamellar phospholipid liposomes. Demonstrated through pharmacokinetic and toxicological analysis the therapeutic potential of liposomal CCNU, compared to the free drug, by in vitro culture methods and in vivo studies in an adapted animal tumor model.
• Conducted pharmacokinetic data analysis which compared the distribution and exposure of the liposomal analgesic agents morphine and sufentanil to free drug after epidural administration in a cannulated pig model. Developed a novel HPLC assay to detect the aminoglycoside antibiotic G418 in mouse tissue after systemic administration of the drug in free or liposomal formulation.
• Proficient on HPLC, In Vitro tissue culture, animal tumor models, and WinNonlin - Industry-Standard PK/PD Modeling and Analysis.

1990-1993: Medical Laboratory Technician - Saint Peter Hospital, Olympia, WA Clinical Laboratory

• Performed stat and routine clinical analysis in the departments of: Blood banking, hematology, clinical chemistry, coagulation, urinalysis, microbiology, and phlebotomy.

Selected Presentations

• Fjord til Bord: Circulating contaminant and fatty acid levels in coronary heart disease patients after a controlled diet of preferentially farmed Atlantic salmon (Salmo salar), Norwegian Research Council (project project #154738130). Poster presentation and abstract at the Fish meal and oil replacement (FORM, EU A5TN-2002-00628) May 2005, Utrecht, Netherlands. Oral presentation and 4 page short paper at the 25th International Symposium on Halogenated Environmental Organic Pollutants and POPs, Toronto, Canada, August 2005.
• Current levels of primary polybrominated diphenyl ethers (PBDEs) in Norwegian seafood. Four page short papers, with a poster presentation at the 24th (2004, Berlin, Germany) and an oral presentation at the 25th International Symposium on Halogenated Environmental Organic Pollutants and POPs, Toronto, Canada.
• Development of analytical methods and the determination of brominated flame retardants in feed and seafood. Eleventh International Symposium on Nutrition and Feeding in Fish, poster May 2004.
• Poster presentation at the annual meeting of the Controlled Release Society (CRS) June 25, 2001.
• Posters at the national and western regional conferences of the American Association of Pharmaceutical Scientists (AAPS) November 1994, 1996, 1997 and April 1998.

Selected Publications

• Bethune,C., Seljeflot, I., Johansen,O., Arnesen, H., Meltzer, HM., Rosenlund G, Seierstad, SL., Fr�yland, L. and A-K Lundebye. Dietary intake of differently fed salmon; a preliminary study on contaminants. European Journal of Clinical Investigation, 36: 193-201 (2006).
• Bethune, C., Julshamn, K., and Lundebye, A-K. A preliminary comparison of Polybrominated diphenyl ethers to lipid content and levels of polychlorinated biphenyls and dioxins in norwegian-farmed atlantic salmon (salmo salar). International Journal of Food Science and Technology, 40: 143-148 (2005).
• Bethune, C., Neilsen, J., Lundebye, A-K., and Julshamn, K. Current levels of primary polybrominated diphenyl ethers (PBDEs) in Norwegian seafood. Organohalogen Compounds 66: 3814-3819 (2004).
• Bethune, C., Bernards, CM., Shen, DD., Bui-Nguyen, T., Ho, RJY. The role of drug-lipid interactions on the disposition of liposome-formulated opioid analgesics in vitro and in vivo. Anesthesia & Analgesia 93(4): 928-933 (2001).
• Bethune, C, Geyer RJ, Spence AM, Ho RJ. Lipid association improves the therapeutic index of lomustine [1-(2-chloroethyl)-3-cyclohexyl-1- nitrosourea] to suppress 36B-10 tumor growth in rats. Cancer Research 61(9): 3669-74 (2001).
• Bethune, C., Blum, A., Geyer, RJ., Silber, JR., Ho, RJY. Lipid association increases the potency against primary medulloblastoma cells and systemic exposure of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in rats. Pharmaceutical Research 16(6): 904-911 (1999).
• Bethune, C., Bui, T., Liu, ML., Kay, MA., Ho, RJY. Development of a high-performance liquid chromatographic assay for G418 sulfate (Geneticin). Antimicrobial Agents and Chemotherapy 41(3): 661-664 (1997).

[last updated: 2006-05-31]

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