Obesity and Pharmacokinetics

Reviewed and revised 6 March 2015

OVERVIEW

• obesity affects all four aspects of pharmacokinetics
• As drug administration based on total body weight can result in in underdosing or overdosing, depending on the characteristics of the drug, weight-based dosing scalars must be considered
• Lean body weight is the optimal scalar for most IV opioids and anaesthetics
• The pharmacodynamic profile of drugs may also be affected, e.g. the risk of respiratory depression and loss of airway patency is greater with sedatives and narcotics
• careful therapeutic drug monitoring is important in obese patients
• morbidly obese people are often excluded from clinical trials during the drug development process so data is limited on the correct dosing of many drugs, and clinical judgement, combined with interpretation of drug pharmacokinetics, is often required

Total Body Weight (TBW) is the patient’s actual weight.

Ideal Body Weight (IBW):

• Males = height – 100
• Females = height – 110

Lean Body Weight (LBW):

• Males = 50 + 0.9kg for every cm over 150cm
• Females = 45 + 0.9kg for every cm over 150cm

ABSORPTION

• increased absorption of oral medications (increased gastric emptying)
• difficult IV access in the obese
• decreased SC absorption due to poor subcutaneous blood supply
• IM administration may fail if needles are too short

DISTRIBUTION

• markedly affected by ratio of adipose tissue to lean body mass if lipid soluble
• increased Vd of lipid soluble drugs
  -> dose lipid soluble drugs on actual body weight
  (remifentanil is an exception, although lipophilic Vd does not change – use IBW or LBW)
• no change in Vd of H2O soluble drugs (but blood, ECF, body organ and connective tissue volume are also increased)
  -> dose on ideal or lean body weight
• accumulation of lipophilic drugs in fat stores
• may increase dose required to gain effect
• total body water may be increased by resuscitation volume
• Cmax reduced
• altered protein binding

METABOLISM

• variable effects
• increases in cytochrome P450 2E1 activity and phase II conjugation activity
• more likely to be affected by critical illness with drug interactions
• reduced hepatic blood flow

ELIMINATION

• T1/2 increased of lipid soluble drugs due to accumulation
• obese patients with normal renal function have increased GFRs
  -> increased clearance of drugs excreted by the kidneys
• co-existing disease will effect this (e.g. nephropathy associated with diabetes and hypertension)
• calculated and measured creatinine clearance correlate poorly in obesity and in critical illness

DOSING

Dosing of common anaesthetic drugs in the obese

References and Links

LITFL

• CCC – Obesity and trauma
• CCC – Obesity and Critical Illness
• CCC – Complications of Obesity
• CCC – Obesity and Pharmacokinetics
• CCC – Nutrition of the Critically Ill Obese Patient
• CCC – Bariatric patient hot case

Journal articles and textbooks

• De Baerdemaeker LEC, Mortier EP, Struys MMRF. Pharmacokinetics in obese patients  Contin Educ Anaesth Crit Care Pain 2004; 4 (5): 152-155. [Free Full Text]
• Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med. 2004 Jan;30(1):18-32. PMID: 14625670.
• Green B, Duffull SB. What is the best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol. 2004 Aug;58(2):119-33. PMC1884581.
• Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49(2):71-87. PMID: 20067334.
• Ingrande J, Lemmens HJM. Dose adjustment of anaesthetics in the morbidly obese. BJA. 2010; 105 (suppl 1): i16-i23. [Free Full Text]
• Leykin Y, Miotto L, Pellis T. Pharmacokinetic considerations in the obese. Best Pract Res Clin Anaesthesiol. 2011 Mar;25(1):27-36. PMID: 21516911.
• Medico CJ, Walsh P. Pharmacotherapy in the critically ill obese patient. Crit Care Clin. 2010 Oct;26(4):679-88. PMID: 20970057.