Doctors and pharmacists often do not take obesity into account when prescribing medication. For this, more insight into the influence of obesity on the distribution and elimination of drugs is of the utmost importance. This is emphasized by Catherijne Knibbe in the most recent issue of the Annual Review of Pharmacology and Toxicology.
Effect of drugs unpredictable
People who suffer from extreme obesity have as a rule undergone physical changes that can impact the uptake, distribution and elimination of drugs. These changes require individualized dosing, advises Catherijne Knibbe, Leiden Professor of Individualized Drug Treatment. Her publication appeared on 6 January in the prestigious journal Annual Review of Pharmacology and Toxicology.
Obesity leads to an enlarged heart, wider blood vessels and a larger blood volume. This in turn leads to effects such as an increase in bloodflow through the liver, as a result of which the elimination rate of certain drugs may increase. In addition, altered body composition in obese people may also lead to a highly different distribution of the drug throughout the body.
Customised drug dose
Knibbe warns: ‘Obese patients are often prescribed a standard drug dose, or doctors and pharmacists tend to automatically assume that these people need a higher dose. However, that is not necessarily the case. Moreover, a higher dose can also be harmful. For example, obese people are more likely to suffer from sleep apnoea: they do not breathe well when they sleep. We have to think carefully before giving these patients a higher dose of sedatives or morphine.’
Research in obese patients
To optimally treat obese patients, research is required to gain insight into how drugs are distributed and eliminated from the body. This is what Knibbe, a clinical pharmacologist, does at the St. Antonius Hospital in Nieuwegein, Utrecht, where she works. After administering the usual dose, blood samples are taken from the patient. These samples provide information on the uptake, distribution and breakdown of active substances in the body. The optimal dose in obese patients can be derived from these studies.
Cefazolin concentrations versus time after a 2 g dose in morbidly obese patients (grey) and non-obese patients (black) in (a) subcuteanous tissue (ISF fluid) and (b) plasma. Figure reprinted from Brill et al, J Antimicrob Chemother. 2014
Knibbe, C.A. et.al., Drug Disposition in Obesity: Toward Evidence-Based Dosing, Annual Review of Pharmacology and Toxicology, DOI: 10.1146/annurev-pharmtox-010814-124354, published online 17 October 2014.
Source: Leiden University