How Does Obesity Alter Pharmacokinetics in Kids?

Jessica C. Stovel, RPh

Disclosures

August 22, 2013

Question

Does obesity affect medication pharmacokinetics in children?

Response from Jessica C. Stovel, RPh, Adjunct Assistant Professor, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

There are few data discussing the impact of obesity on the pharmacokinetics of medications commonly used within the pediatric population.[1,2] As such, there is much uncertainty and few practical recommendations.[1] Some important considerations are discussed below.

Absorption

Obesity is unlikely to affect absorption, but more research is needed to elucidate possible effects.[3]

Volume of Distribution

One can generally assume that 75% of the excess weight present in obesity is fat mass and 25% is lean mass.[1] The amount of fat and lean mass, which changes throughout childhood, will alter a medication's volume of distribution (Vd).[1]

In obese children, lipophilic medications may or may not have a higher Vd due to drug-specific distribution in adipose tissue.[1,3] Hydrophilic medications may be altered in obese children due to differences in lean body mass, blood volume, and a decreased percentage of total body water.[3,4] As a consequence, hydrophilic medications may have a lower Vd than that found in healthy-weight children.[3]

Plasma Protein Levels

Plasma protein levels may be altered in obesity.[1] Although this type of change could, in theory, affect medications that bind to these proteins, no clinical influence has been observed.[1,5]

Drug Metabolism

Nonalcoholic fatty liver disease may occur in obese children[6] and such liver disease could alter hepatic metabolism. For example, phase 1 (eg, oxidation) and phase 2 (eg, conjugation, glucuronidation, sulfation, acetylation) reactions could increase or remain unchanged.[7] The true influence of childhood obesity on these metabolic pathways is unknown.[3]

Renal Elimination

The effect of obesity on renal clearance is unpredictable.[2] However, it has been observed that kidney size and renal blood flow increase as size increases.[1,3] As such, medications that are eliminated primarily via the kidney may need to be administered more frequently in order to ensure that adequate therapeutic concentrations are reached.[4,7]

Conclusion

Clinicians should consider the theoretical effects that obesity may have on pharmacokinetics when selecting medications for obese children. In addition, organ function, comorbidities, and the illness should be considered.[3] Close patient monitoring and therapeutic drug monitoring (ie, drug levels), if applicable, are advised for safe medication use in obese children.[8]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....