Table 1

Potential impact of obesity on pharmacokinetic parameters

Likely effect on pharmacokinetic parameterDosing recommendation
Change in obesityVolume of distributionClearanceLoading doseMaintenance dose
Body composition
 Fat mass↔ or ↑*Hydrophilic drugs – dose according to IBW (+ % increase)Dose according to LBW or BSA (calculated using actual body weight)§
Lipophilic drugs – dose according to TBW
 Lean mass↔ (or ↑)
 Liver function (non-alcoholic fatty liver disease)↔ or ↓↔ or ↓No recommendation**
 Renal function↔ or ↑††,‡‡↔ or ↑No recommendation**
Plasma binding proteins
 Albumin††No change§§
 α-1 acid glycoproteins↔ or ↑††↔ or ↑¶¶↔ or ↑***No change§§
Regional blood flow↔ or ↓No recommendation**
  • * Exceptions may be drugs metabolised by CYP2E1 which is expressed in adipose tissue.6

  • Accounting for extra water in lean tissue.9

  • Use caution since many lipophilic drugs do not distribute extensively into adipose tissue in vivo. Consider administering loading doses calculated on total body weight as a series of mini-loading doses.

  • § See Han et al.26

  • Hypothetical since there are no drug metabolism data.

  • ** Insufficient data.

  • †† Conflicting reports.6

  • ‡‡ Healthy obese subjects, whereas comorbidity such as type II diabetes or hypertension impairs renal function.

  • §§ There are some rare exceptions and the reader is directed to a review by Benet and Hoener.14

  • ¶¶ For drugs with a volume of distribution ≥30 l.14

  • *** Increased with low extraction ratio drugs.14

  • BSA, body surface area; IBW, ideal body weight; LBW, lean body weight; TBW, total body weight.