Pharmacist’s Cheat Sheet for Obese Patients:

I. Introduction:

Obesity
● defined as a body mass index (BMI) of 30 or higher (WHO) and has been recognized as a disease
requiring a range of medical interventions to advance treatment and prevention (AMA, 2013).

● Obesity is linked to several health problems, including hypertension, cardiovascular disease, type II
diabetes mellitus (T2DM), respiratory complications, hepatic steatosis, chronic pain, and depression.

● Obesity leads to high total body weight (TBW), which is attributed to increased adipose tissue mass as
well as lean body weight (LBW). As an individual’s weight increases, his or her body composition
changes, resulting in higher LBW and disproportionately higher adipose content.

● Large body mass causes increased blood volume and cardiac output in obese individuals, which is
required for adequate oxygen and nutrient supply

Table 1: Classification of Obesity Based on Body Mass Index (BMI)

Classification BMI (kg/m2)

Underweight <18.5

Normal Body Weight 18.5–24.9

Overweight 25–29.9

Obese 30–39.9

Morbidity Obese ≥40

Figure 1: Body Composition in a Normal-weight and Obese-Patients (Barras, M. 2017)

II. Pharmacokinetics in the Obese
a. Administration
● Obesity does not significantly alter oral absorption, but parenteral absorption can be affected
due to increased subcutaneous tissue thickness and higher BMI.
● Cardiac output affects organ perfusion, which may alter drug delivery to target tissues.
● The protein binding properties of a drug affect its transport in blood and permeability into
tissues.
● Changes in albumin and α1 acidic glycoprotein reported in obese patients can affect the rate at
which the drug is taken up from the circulation.
● Absorption is dramatically altered in obese individuals following gastric bypass, which leads to
decreased gastric mixing and mucosal absorption along a shortened surface area.
b. Distribution
● The volume of distribution is related to structural aspects of the body. Hydrophilic drugs
generally have a high plasma concentration relative to dose, and a smaller volume of
distribution. In contrast, lipophilic drugs distribute more readily into adipose tissue, resulting in
lower plasma concentrations and a larger volume of distribution.
● Hydrophilic drugs typically remain in extracellular fluid and their volume of distribution correlates
with lean mass.
● Lipophilic drugs, the volume of distribution is more likely to correlate with total body weight.
Highly lipophilic drugs distribute extensively into adipose tissue, resulting in a larger volume of
distribution compared to less lipophilic drugs.
● Drugs with a large volume of distribution often require loading doses followed by a constant
dose rate to maintain steady-state plasma concentrations. Steady-state concentrations are
dependent on drug clearance.
c. Metabolism
● Obesity results in altered drug metabolism and a state of low-grade chronic inflammation that
can result in obesity-related metabolic disorders.
● Phase I and II enzyme activities in obesity may be affected by the fatty infiltration of the liver and
its associated changes.
 d. Renal Elimination
● Clearance is correlated to lean rather than adipose weight as adipose tissue has little metabolic
activity.
● As clearance determines a drug’s maintenance dose, clinicians should consider how lean body
weight, rather than total body weight, impacts dosing.
● When lean body weight increases there will be a corresponding increase in drug clearance and
an increased dose may be required.
● Kidney hyperfiltration is observed early on in obesity, which enhances drug elimination and
results in suboptimal drug levels.

III. Dosing Considerations in Obese Patients

Principles of drug dosing for obese patients may be adopted to calculate loading dose and maintenance dose.

A. Loading Dose
● The loading dose is primarily based on VD.
● In general, the weight used to calculate the loading dose depends on how the drug is distributed
in the lean and fat tissues in the body;
○ If the drug is primarily distributed into the lean mass, IBW will be used to calculate the
loading dose.
○ If the drug is largely distributed into the fat tissues, TBW will be used.
○ If the distribution is somewhere in between, an adjusted weight may be used (Allen,
2008).

B. Maintenance Dose
● The maintenance dose primarily depends on drug clearance (Cl).
● The most commonly used equations to estimate glomerular filtration rate (GFR) are the
Cockcroft–Gault (CG) equation (Cockcroft and Gault, 1976) and the Modification of Diet in
Renal Disease (MDRD) equation (Levey et al, 1999).

Clcreat.obese = [(140 – age) × (Weight in kg)]/[72 × serum creatinine] × 0.85 if female

Table 2: Drugs with Altered Pharmacokinetic Parameters in Obesity (Ritschel, W.A)

Drug Elimination Volume of Total
Half-life Distribution Clearance

Acetaminophen ↓ ↓ ↓

Acetylprocainamide ↓ ? ↓

Amikacin ↓ ↓ ↓

Antipyrine ↑ ↓ ↓

Caffeine ↑ ↑ U

Diazepam ↑ ↑ ?

Digoxin ↓ ↓ ↓

Fentanyl ↑ ↑ U
Gentamicin ↓ ↓ ↓

Procainamide ↓ ↓ U

Theophylline ↑ ↓ ↓

Thiopental ↑ ↑ ↓

Tobramycin ↓ ↓ ↓

Vancomycin ↓ ↑ ↑

Note: ↑= increase; ↓=decrease; U= unchanged

Table 3: Drugs that Require Dose Adjustment in Obesity (Barras, M. 2017)

Drug Patient Monitoring*

Low-molecular-weight heparins (enoxaparin, TDM - anti-Xa monitoring, clinical response

dalteparin)

Digoxin TDM - serum digoxin, clinical response

Phenytoin TDM - serum phenytoin, clinical response

Acyclovir Clinical response

Antibiotics - macrolide (erythromycin+), Clinical response, microbiological response

fluoroquinolone (ciprofloxacin+)

Antibiotics - glycopeptides (vancomycin), TDM - all, clinical response, microbiological response

aminoglycosides (gentamicin, tobramycin), bata-
lactams+(penicillins, cephalosphorins)

Antifungals (amphotericin, voriconazole, fluconazole) TDM - serum voriconazole, clinical response,

microbiological response

Unfractionated heparin TDM - aPTT monitoring, clinical response

Monoclonal Antibodies TDM - clinical response

Ciclosporin TDM - serum cyclosporine, clinical response

Note: TDM=therapeutic drug monitoring; aPTT=activated partial thromboplastin time; *=response refers to
both effectiveness or adverse effects; += dose adjustment is generally required at high intravenous doses

IV. Formulas and Sample Problem

Body Size Descriptors Used to Calculate Drug Doses (William Clarke, Amitava Dasgupta)
Measurement Formula Gender

Total Body Weight (TBW), kg (*patients actual weight)

 Ideal Body Weight (IBW), kg Devine’s estimation
=45.4 + 0.89 x (height (cm) - 152.4) + 4.5 (if male)

Adjusted Body Weight (Adj. BW), kg 0.4 x (TBW – IBW) + IBW

Lean Body Weight (LBW2005), kg James equations:

1.1 x TBW (kg) - 0.0128 x BMI x TBW (kg) Males
1.07 x TBW (kg) - 0.0148 x BMI x TBW (kg) Females

Janmahasatian formulae:
(9.27x103 x weight (kg))/(6.68x103 + 216 x BMI) Males
(9.27x103 x weight (kg))/(8.78x103 + 244 x BMI) Females

Body Surface Area(BSA) TBW (kg)0.425 x height (cm)0.725 x 0.007184

Body Mass Index (BMI) [Weight (kg)/height (cm)2] × 10,000 (cm2/m2)

Calculating Drug Doses

The clinical issue is that calculating drug doses using each body size descriptor will result in a different weight.
Consider dosing a 150 kg man who is 170 cm tall. Rounded to the nearest 5 kg, his body size descriptors are:
● total body weight = 150 kg
● lean body weight = (9270 x 150) / 6680 + 216 x (150/1.72) = 80 kg
● ideal body weight = 45.4+0.89x(170–152.4)+4.5=65kg

Large variations exist for mg/kg dosing depending on which metric is used.

Clinical Example of Estimating Creatinine Clearance in Obesity

Problem #1:

A 50-year-old female, BT, was admitted to the hospital with sepsis. Her height is 5 feet and 5 inches, and
weight was 350 lb. Her serum creatinine is 1.2 mg/dL. The team has decided to start BT on an antibiotic
regimen.
Discussion:
● •First, calculate BMI for BT., Her TBW in kilogram = 350 (lb)/2.2 (lb/kg), which is 159.1 kg. Her height in
centimeter (cm) = 65 (inches) × 2.54 (cm/inch), which is 165.1 cm
Her BMI = 58.4 kg/m2

● She is morbidly obese, according to the classification of obesity based on BMI. It is recommended to
use adjusted body weight to estimate Clcr from the CG equation for patients who are overweight,
obese, or morbidly obese.

● In order to calculate Adj. BW, IBW needs to be calculated first. IBW = 45.5 + 2.3 × [Height (inches) –
60] kg
Her IBW = 57 kg

● Calculate Adj. BW. Adj. BW = IBW + 0.4 × (TBW – IBW) kg

Her Adj. BW = 97.8 kg
 ● Calculate Clcr (mL/min) by CG equation using Adj. BW: Clcr (mL/min) = [(140-age) × (Weight in kg)]/
[72 × serum creatinine] × 0.85
Her estimated Clcr = 87 mL/min

V. References

1. Ritschel, W (1992). Handbook of Basic Pharmacokinetics

2. Leon Shargel, Andrew Yu. Applied Biopharmaceutics and Pharmacokinetics. The McGraw-Hill
Companies.
3. William Clarke, Amitava Dasgupta. Clinical Challenges in Therapeutic Drug Monitoring. Elsevier Inc.
4. Morish, G.A, Pai, M.P, Green, B., 2011. The effects of obesity on drug pharmacokinetics in humans.
Expert Opinions on Drug Metabolism and Toxicology. 7(6):697-706
5. Barras, M. 2017. Drug dosing in obese patients. Australian Prescriber. 40(5):189-193