Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Pharmaceutical Sciences


Interdepartmental Program

First Advisor

Paul Larrat


Background: Medications benefit people with diseases and medical conditions, improving many patients' lives and in some cases significantly increasing their quality of life. Despite these great benefits, medications can lead to serious adverse effects. Adverse drug reactions (ADRs) are the 4th leading cause of death, greater than major killers including pulmonary diseases, diabetes and automobile death. Not all medication groups have the same incidence in inducing diseases. Anti-infective agents - including antibacterial agents- are the most likely to induce diseases followed by cardiovascular agents and antineoplastic agents.

Objectives: Drug safety is a very important issue in patient therapy. Since antibacterial agents in general and fluoroquinolones specifically are among the most prescribed medications, it is very important to quantify their risks in causing serious adverse reactions such as hepatotoxicity and pancreatitis. In terms of drug safety and preventing ADRs, costs are a very important factor because many conditions like hypoglycemia can be prevented, leading to significant decreases in cost and improvement in quality of life. Since there is a dearth of research that has examined these areas, epidemiological studies are needed. The objectives of the three proposed manuscripts of this dissertation were to a) estimate the risk of hepatotoxicity associated with fluoroquinolones use; b) examine antibacterial agents use and the risk of acute pancreatitis development; c) review the healthcare databases in United States and European countries that are commonly utilized in conducting epidemiological research.

Methods: Two matched case control studies were used to examine the risk of hepatotoxicity and acute pancreatitis development with using fluoroquinolones and antibacterial agents, respectively. The Veterans' Affairs (VA) medical database was used to perform the two studies. Odds ratios (OR) and their 95% confidence intervals (CI) were derived from crude and adjusted conditional logistic regression models. In the third paper, a literature search was performed using Publisher Medline (Pubmed), Embase® and the Iowa Drug Information Services (IDIS) to perform a review of four medical databases including the Nationwide Inpatient Sample database, the Veterans' Affairs medical database, the Health Improvement Network database and the Norwegian medical database.

Results: In the first study, fluoroquinolones use was associated with increased risk of hepatotoxicity. However, only ciprofloxacin was statistically significantly associated with development of hepatotoxicity while levofloxacin and moxifloxacin were not associated with hepatotoxicity development. In the second study, use of antibacterial agents was associated with increased risk of acute pancreatitis.

Conclusion: The findings from in both studies show that antibacterial agents are associated with increased risk of hepatotoxicity and acute pancreatitis. Knowing the safety of medication is very important for the clinical practice especially for antibacterial agents since they are commonly used and clinicians are considering these agents very safe. However, further research is needed to confirm these findings and to understand the biological mechanism behind their toxicity.



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