Introduction
Patient’s weight is a crucial consideration in medication dosage since the size of the body affects the concentration of the drug in body fluids and at the site of action. Dose calculation based on body weight became standard for certain medications dosing. Dosing based on patient’s specific weight makes the drug quantity administered specific to the patient being treated. Gender, age, weight, pregnancy, albumin in blood, diet, medication type, gastrointestinal function and kidney function they are all factors altering drug response [1].
Measures of Weight [1]
- Direct: Underwater weighing (hydrodensitometry), Skinfold measurement, Dual-energy x-ray absorptiometry (DEXA) and Bioelectrical impedance analysis (BIA)
- Indirect (Table 1).
Table 1: Measures of Weight [1]
| Body mass index (BMI) | Ideal Body Weight (IBW) | Actual body weight(ABW) | Adjusted body weight
(AdjBW) |
Lean body weight(
LBW) |
Body Surface Area(BSA) | Predicted normal weight (PNWT) |
| Equation: kg/m² WHO’s
preferred measure for classifying obesity: Pre-obesity: BMI 25–29.99 kg/m²
Obesity class I: BMI30–34.99 kg/m²
Obesity class IIBMI 35– 39.99 kg/m²
Obesity class III(morbid obesity) : BMI ‡40 kg/m² |
Female: 45.4 kg+0.89X(Ht in cm-152.4)
Male: 49.9 kg+0.89X(Ht in cm-152.4 |
This is a patient’s real weight Called total body weight (TBW)
|
AdjBW (kg) = IBW + 0.4 (TBW – IBW)
|
The patient’s weight excluding fat
Males: LBW=(9270 xTBW) /(6680 +216 xBMI) Females: LBW=(9270 xTBW) /(8780 +244 xBMI) |
BSA (m2) = (TBW)0.425X(height in cm)0.725 X 0.007184
BSA (m2) = [(TBW) X(height in cm)/3600]½ |
Predict the expected normal weight of an overweight or obese individual
Males: PNWT(kg) = 1.57xTBW 0.0183xBMI x TBW- 10.5
Females: PNWT (kg) = 1.75xTBW – 0.0242x BMI x TBW – 12.6 |
How Does a Person’s Body Weight Affect Drug Response (Drug Distribution and Metabolism)
After a drug is absorbed into the bloodstream, it rapidly circulates through the body. The average circulation time of blood is 1 minute. As the blood recirculates, the drug moves from the bloodstream into the body’s tissues for example: fat, muscle, and brain tissue. Once absorbed, most drugs do not spread evenly throughout the body. Drugs that dissolve in water (water-soluble drugs), tend to stay within the blood and the fluid that surrounds cells .Drugs that dissolve in fat (fat-soluble drugs), tend to concentrate in fatty tissues. Other drugs concentrate mainly in only one small part of the body for example: iodine concentrates mainly in the thyroid gland; because the tissues have a special attraction for affinity and the ability to retain that drug. Factors affecting drug distribution: plasma protein binding, physicochemical properties of the medication (lipophilicity, hydrophilicity), tissue blood flow and membrane transporters. Body composition in a normal body weight and obese patients, 20% from normal body weight is adipose weight and 80% lean weight, however, 40% from obese patient weight is adipose tissue and 60% is lean weight. Hydrophilic drugs excreted by renal clearance, has low volume of distribution, low Intracellular penetration and high extracellular distribution in comparison to lipophilic drugs that are excreted by hepatic clearance has high volume of distribution, high Intracellular penetration and low extracellular distribution [2-7] (Tables 2 and 3).
Table 2: Hydrophilic and Lipophilic medications [2,4,5]
| Medication | Hydrophilic | Lipophilic |
| Deferoxamine | Yes | No |
| Benzodiazepines | No | Yes |
| Tricyclic antidepressants | No | Yes |
| Aminoglycosides | Yes | No |
| Amphotericin-B | No | Yes |
| Vancomycin | Yes | No |
| Tigecycline | No | Yes |
| Rocuronium | No | Yes |
| Rifampicin | No | Yes |
| Sucrose | Yes | No |
| Atorvastatin,simvastatin | No | Yes |
| Propofol | No | Yes |
| Sufentanil | No | Yes |
| Thiopental | No | Yes |
| Rosuvastatin,pravastatin | Yes | No |
| B-lactam
Carbapenem Cephalosporins Penicillin |
Yes | No |
| Daptomycin | Yes | No |
| Atenolol | Yes | No |
| Thiazide diuretics | No | Yes |
| Acyclovir | Yes | No |
| Voriconazole | No | Yes |
| Low molecular weight heparin | Yes | No |
| Lithium | Yes | No |
| Fentanyl | No | Yes |
| Phenytoin | No | Yes |
| Atenolol | Yes | No |
| Sotalol | Yes | No |
| Steroids | No | Yes |
| Fluoroquinolones | No | Yes |
| Macrolides | No | Yes |
| Warfarin | Yes | No |
| Linezolid | No | Yes |
| Tetracycline | No | Yes |
| Clindamycin | No | Yes |
| Captopril, Perindopril, Lisinopril, Enalapril | Yes | No |
| Fosinopril , Ramipril | No | Yes |
Table 3: Weight based medications [6-7]
| Medication | Dosing weight | ||
| Normal weight | Obese | ||
| GCSF(Filgrastim) | Actual body weight | Actual body weight | |
| Procainamide | Ideal body weight | Ideal body weight | |
| Erythromycin | Ideal body weight | Ideal body weight | |
| Phenytoin | Ideal body weight | LD: AdjBW
MD: IBW |
|
| Fluconazole | Ideal body weight | Total body weight | |
| Thiopental | Ideal body weight | LD: IBW
MD: ABW |
|
| Succinylcholine | Ideal body weight | Total body weight | |
| Rocuronium | Ideal body weight | Ideal body weight | |
| Vecuronium | Ideal body weight | Ideal body weight | |
| Propofol | Total body weight | Induction: IBW
Maintenance: AdjBW |
|
| Heparin | Ideal body weight | Adjusted body weight | |
| Enoxaparin | Ideal body weight | DVT treatment: ABW | |
| Isoniazid | Ideal body weight | Ideal body weight | |
| Ethambutol | Lean body weight | Ideal body weight | |
| Pyrazinamide | 40-55 kg → 1000 mg once daily
56-75 kg → 1500 mg once daily 76-90 → 2000 mg once daily |
Ideal body weight | |
| Rifampin | Ideal body weight | Ideal body weight | |
| Lidocaine | Ideal body weight | Ideal body weight | |
| Lorazepam | Ideal body weight | LD: ABW
MD: IBW |
|
| Midazolam | Ideal body weight | Initial dose: TBW
Continuous dose: IBW |
|
| Acyclovir | Ideal body weight | Ideal body weight | |
| Aminoglycosides | Ideal body weight | Adjusted body weight | |
| Vancomycin | Initial dose: Total body weight, then adjusted according trough concentration | Adjusted body weight | |
| Polymyxin B | Ideal body weight | Adjusted body weight | |
| TMP/SMX | Total body weight | Adjusted body weight | |
| Liposomal amphotericin B | Total body weight | Adjusted body weight | |
| Voriconazole | Total body weight | Adjusted body weight | |
| Flucytosine | Ideal body weight | Ideal body weight | |
| Ganciclovir | Total body weight | Adjusted body weight | |
References
- Hanley, Darrell RA, David JG (2010) Effect of Obesity on the Pharmacokinetics of Drugs in Humans. Clin Pharmacokinet 49: 71-87. [crossref]
- John M. Benson ((2017)) Antimicrobial Pharmacokinetics and Pharmacodynamics in Older Adults. Infect Dis Clin N Am 31: 609-617.
- Michael Barras (2017) Dosing in Obese Adults. Aust Prescr 40: 189-193. [crossref]
- Reflection paper on investigations of pharmacokinetics and pharmacodynamics in the obese population EMA/CHMP/535116/2016.
- Kenneth JM, Sanjay G, Rudra P, Ellen SOM, Shiva G et al. (2010) Antihypertensive medications and risk of community acquired pneumonia. Journal of Hypertension 28: 401-405. [crossref]
- Janson B, Thursky K (2012) Dosing of antibiotics in obesity. Curr Opin Infect Dis 25: 634-649.
- Polso AK, Lassiter JL, Nagel JL (2014) Impact of hospital guideline for weight-based antimicrobial dosing in morbidly obese adults and comprehensive literature review. J Clin Pharm Ther 39: 584-608. [crossref]