Unraveling the drivers of antimicrobial pharmacokinetic variability in individuals with obesity and hospitalized patients with multimorbidity

Rhee, K.P. van (2025)

Doctoral Thesis

Obesity may alter how a person absorbs, distributes, metabolizes or excretes medication. This thesis describes how obesity affects drug levels in the blood for antimicrobial agents, such as ciprofloxacin and fluconazole. For ciprofloxacin the influence of multimorbidity, e.g. ICU-patients with obesity or gastrointestinal mucositis in hematology patients, on drug levels is also explored. The studies show that men with severe obesity excrete fluconazole more quickly, increasing the risk of treatment failure which requires a higher loading dose. For ciprofloxacin, higher doses are advised for obese patients when impaired tissue treating is anticipated. The influence of obesity on drug metabolism is unpredictable, making it difficult to determine if standard dosing regimens are appropriate for severely obese patients. This lack of information can lead to underdosing, reducing effectiveness, or overdosing, increasing side effects. The findings highlight the need to study obese individuals during drug development, as is already done for people with liver/kidney issues, children, and the elderly. Research in a small group of severely obese individuals can provide valuable insights to determine whether weight-based or fixed dosing regimens are more appropriate for new drugs.

• Obesity
• Pharmacokinetics
• Antibiotics
• Antifungals
• Special patient population

• All authors: Rhee, K.P. van
• Supervisor: Knibbe, C.A.J.; Brüggemann, R.J.M.
• Co-supervisor: Linden, P.D. van der
• Committee: Hasselt, J.G.C. van; Irth, H.; Koch, B.C.P.; Lange, E.C.M. de; Roon, E.M. van
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2025-02-19
• ISBN (print): 9789465104126
• Sponsorship: St. Antonius Onderzoeksfonds; Tergooi MC wetenschapsfonds