Table 1

Potential impact of obesity on pharmacokinetic parameters

		Likely effect on pharmacokinetic parameter		Dosing recommendation
	Change in obesity	Volume of distribution	Clearance	Loading dose	Maintenance dose
Body composition
Fat mass	↑	↔ or ↑	↔^*	Hydrophilic drugs – dose according to IBW (+ % increase^†)	Dose according to LBW or BSA (calculated using actual body weight)^§
Fat mass	↑	↔ or ↑	↔^*	Lipophilic drugs – dose according to TBW^‡
Lean mass	↑	↔ (or ↑^†)	↑
Physiological
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.