Drug dosing in infants, elderly and obese patients, how their pharmacokinetics is different from normal adult and formulae to calculate the dose.

1. DRUG DOSING IN INFANTS,
ELDERLY AND OBESE
PATIENTS.
BY JAVVAD HASAN

2. DRUG DOSING IN INFANTS AND
CHILDREN.
■ Infants and children have different dosing requirements
than adults.
■ Pediatric age range is defined as ages 0-18. US FDA
classified them as:
1. preterm newborn infant ,
2. newborn infant (birth to 28 days),
3. infant (28 days to 23 months)
4. young child (2 to 5 years),
5. older child (6 to 11 years),
6. adolescent(12 to 18 years).

3. ■ For convenience, “infants” are here arbitrarily defined as
children 0 to 2 years of age.
■ Special consideration is necessary for infants less than 4
weeks (1 month) old.
■ Their ability to handle drugs often differs from that of
more mature infants.
■ The variation in body composition and the maturity of liver
and kidney function are potential source of differences in
pharmacokinetics with respect to age

4. PHARMACOKINETICS
■ Absorption : infants have reduced gastric acid secretion,
therefore the extent of drug absorption is altered and less
predictable.
■ Distribution is also affected by a decreased protein-binding
capacity in newborns, and particularly in pre-term
newborns, therefore leading to increased levels of the
active free drug for highly protein-bound drugs.
■ The blood-brain barrier in the newborn is functionally
incomplete and hence there is an increased penetration of
some drugs into the brain.

5. ■ Renal excretion • Drug excretion by the kidneys is mainly
dependent on glomerular filtration and active renal tubule
secretion. Pre-term infants have approximately 15% (or
less) of the renal capacity of an adult, , but this matures
rapidly to about 50% of the adult capacity by the time they
are 4-5 weeks old.
■ At 9-12 months of age, the infant’s renal capacity is equal
to that of an adult.

6. PAEDIATRIC DOSE CALCULATION
A. Dose calculation related to age:
1. Young`s rule
2. Dilling`s rule
3. Fried`s rule
B. Dose calculation related to Weight:
1. Clarke`s rule
C. Dose calculation related to body surface area.

7. DOSE CALCULATION RELATED TO AGE
1. Young's rule
Child’s dose = [ Age (yrs)/ Age(yrs) + 12 ] × adult dose.
Example : The pediatric dose for a 9-year old child who weighs
63lbs needs to be determined. You learn that the adult dose for
the same drug is 200mg. Using Young’s rule, what dose should the
child be given?
By using the Young’s formula:
Child’s dose = [9 / (9 + 12)]× 200mg
Child’s dose = [9 / 21]× 200mg
Child’s dose = 200mg x 0.43
Child’s dose = 86mg.

8. 2. Dilling's rule
Child dose = [ Age (Yr)/ 20] × adult dose
Example: What will be the dose of a child of 10yrs If the
adult dose of a drug is 600mg?
So, by applying the Dilling’s formula
Child dose = [10/20] × 600 mg
Child dose = 300mg.

9. 3. Fried’s rule.
Child dose= [ Age( month) / 150] × Adult dose.
Example: If an adult’s dose of a particular medication is 50
mg, what is the dosage for a 10-month-old infant?
By applying fried’s rule :
Child dose = [10/150] × 50
Child dose= 10/3
Child dose= 3.33 mg

10. DOSE CALCULATION RELATED TO
WEIGHT
Clark’s rule
Child dose= [Body weight(lb) / 150 ] × adult dose
Child dose = [ body weight (kg) / 70] × adult dose
(1kg = 2.2 lb)
Example: The average adult dose for a drug is 250mg. Using
Clark’s rule, what dose should be given to an 8-year old child
who weighs 57lbs?

11. So by applying Clark’s rule:
Child dose = [ 57/150] × 250mg
Child dose = 0.38 × 250 mg
Child dose = 95mg

12. DOSE CALCULATION BASED ON BODY
SURFACE AREA
Child dose= [ Child’s body surface area / Average adult body
surface area] × Adult dose
(An average adult of 70kg, 175cm has a body surface area of
1.73m2. Child body surface area obtained from nomogram
that determine body surface area using the height (cm or in)
and weight (kg or lb) of the child.)

14. Example : calculate the dose for a child weighing 75lbs and is
50inches tall and the normal adult dose is 25mg.
So first of all find the body surface area of child from
nomogram
By applying the formula
Child dose= [ 1.03/1.73] × 25mg
Child dose = 0.59 × 25 mg
Child dose = 14.75mg

15. DRUG DOSING IN ELDERLY PATIENTS
■ Defining “elderly” is difficult.
■ The geriatric population is often defined as patients who
are older than 65 years,
■ In addition, there is an increasing number of people who
are living more than85 years, who are often considered as
the “older elderly“ population.
■ The aging process is more often associated with
physiologic changes during aging rather than purely
chronological age.
■ According to WHO, the elderly have been classified as the
■ young old (ages 65-75 years),

16. ■ The old (ages 75-85 years),
■ and the very old (age > 85 years).

17. PHARMACOKINETICS
■ Performance capacity and the loss of homeostatic reserve
decreases with advanced age
■ Several vital physiologic functions like renal plasma flow,
glomerular filtration, cardiac output, and breathing
capacity can drop from 10% to 30% in elderly subjects
compared to those at age 30.
■ The physiologic changes due to aging may necessitate
special considerations in administering drugs in the elderly.
■ Age causes alterations in the quantity and quality of target
drug receptors , leading to enhanced drug response.

18. ■ Quantitatively, the number of drug receptors may decline
with age,
■ Qualitatively, a change in the affinity for the drug may
occur.
■ Increases in adverse drug reactions are due to physiologic
changes in drug absorption, distribution, and elimination,
including renal excretion and hepatic clearance.
■ Age-dependent alterations in drug absorption may include
a
1. decline in the splanchnic blood flow,
2. altered gastrointestinal motility,
3. increase in gastric pH,
4. alteration in the gastrointestinal absorptive surface.

19. ■ Drug protein binding in the plasma may decrease as a
result of decrease in the albumin concentration,
■ Apparent volume of distribution may change due to a
decrease in muscle mass and an increase in body fat.
■ Renal drug excretion generally declines with age as a result
of decrease in the glomerular filtration rate.
■ Enzymes responsible for drug biotransformation may
decrease with age, leading to a decline in hepatic drug
clearance.
■ Elderly patients may have several different
pathophysiologic conditions that require multiple drug
therapy that increases the likelihood for a drug interaction.
■ Moreover, increased adverse drug reactions and toxicity
may result from poor patient compliance.

20. PRINCIPLES OF DRUG THERAPY IN
ELDERLY
1. Avoid unnecessary drugs.
2. Treat causes, rather than symptoms
3. Collect drug allergy history
4. Choose most efficacious drug with decreased ADRs
5. Choose right dosage forms
6. Avoid polypharmacy.

21. DRUG DOSING IN OBESE PATIENTS
■ Obesity are defined as abnormal or excessive fat
accumulation that presents a risk to health.
■ A body mass index (BMI) over 25 is considered overweight,
and over 30 is obese.
■ BMI is calculated using weight in kg and height in meter.
■ The BMI is calculated by the following formula:
BMI= weight (kg)/height (m)2
■ If a person’s BMI is <18.5kg/m2 they are considered
underweight, 18.6-24.99kg/m2 is normal and >25kg/m2
is overweight. The overweight is again stratified into 4
classes.

22. OVERWEIGHT BMI
Pre obesity 25 – 29.99 kg/m²
Obesity class 1 30-34.99 kg/m²
Obesity class 2 35-39.99 kg/m²
Obesity class 3 >40 kg/m²

23. ■ When the BMI is more than 40kg/m2, it’s known as
morbid obesity.
■ Accurate dosage regimens for obese patients are still
vague.
■ The pharmacokinetics of each person varies with a change
in weight.
■ As the number of obese patients with comorbidities such
as diabetes mellitus and hypertension increases,
physicians will encounter more problems regarding doses
as the normal dose may not show therapeutic effect.
■ The clearance and distribution of obese patients are
different from a normal person

24. PHARMACOKINETICS
■ The pharmacokinetics of an obese person is different from
a normal person
■ Absorption depends on the lipophilicity of the drug.
Adipose tissue does not affect the absorption.
■ Studies show that there is no major alteration in the
absorption in obese patients
■ Lipophilic drugs show increased volume of distribution than
lipophobic or hydrophilic drugs as they are distributed in
the fat tissue and the lean mass.

25. ■ For example volume of distribution of Benzodiazepines is
high Hence TBW should be used.
■ Increased level of serum proteins changes the metabolism
in obese patients that leads to different half-lives of the
drug in an obese patient from a normal person
■ An increase in phase ll metabolism is noticed.
■ Phase l metabolism either increases or remains the same
■ obese patients exhibit higher clearance than non-obese.
■ The kidney weight, renal blood flow glomerular filtration
rate is higher in obese people hence clearance is high.

26. PARAMETERS FOR DOSE CALCULATION
■ To calculate the dosage regimen various formulae or
dosing scales have been formulated.
■ Ideally the dosing formula should consider height, weight,
pharmacokinetic factors etc but so far that kind of formula
doesn’t exist yet.
■ It is mandatory that whenever medications are
administered to an obese patient, especially the ones with
narrow therapeutic index, he or she should be monitored
closely.

27. Some of the commonly used
parameters for dose calculation
include:
Body mass index (BMI) :
■ As explained before, BMI is officially used to obtain dosage
regimens.
■ According to Michael J Henley , BMI is not the most
appropriate dosing scalar because it does not consider
adipose tissue and lean body mass separately .

28. Body Surface Area (BSA): It is calculated using height,
weight and constants as
BSA (m)²= [(TBW)×(height in cm)/3600]½
■ BSA is extensively used in dosing of anti-cancer agents.
■ however its use in calculating drug dose in obese patients
is still questionable.
■ Just like BMI, BSA cannot differentiate between adipose
tissue and lean body mass.

29. Total Body Weight: This method is usually used for normal
patients .
■ Lean body mass and fat depositions do not increase
proportionally in morbidly obese patients .
■ Since majority of the blood supply is goes to regular
muscles instead of adipose tissue, using this method for
calculation may cause toxicity in morbidly obese patients .
■ Ideal Body Weight (IBW): Its equation is based on size
which relates it to mortality of a subject.
■ An empirical equation to estimate IBW was derived by
devine
IBW (kg) = 45.4 kg (49.9 kg if male) + 0.89 × (height in
cm– 152.4)

30. ■ IBW is different from BMI and BSA because it considers
gender while calculating.
■ The use of ideal body weight is limited because it implies
that patients with same height should receive the same
dose and the changes occurring in the body due to obesity

31. Lean Body Weight (LBW): It is the weight of a person
devoid of all the fat mass.
■ It does not take the weight of the adipose tissue into
consideration
LBW (kg) = (9270 × TBW)/(A + B×BMI), where values of A
and B are 6680 and 216 for males, and 8780 and 244 for
females.
Predicted Normal Weight: It is used to predict the
normal weight of an obese individual.
■ It is usually not accurate when height and weight are
extreme.

32. ■ For males, PNWT (kg) = 1.57 ×TBW- 0.0183 ×BMI ×TBW-
10.5.
■ For females, PNWT (kg) = 1.75 ×TBW – 0.0242 ×BMI
×TBW – 12.6
A compilation of drug list along with the formulae that can be
used to calculate dosage regimens is depicted in a table (next
slide)

37. CONCLUSION
Various scales have been formulated to calculate drug dosing
in obese population but more research needs to be done to
get precise doses.

38. REFERENCE
■ World Health Organization. Obesity and overweight [fact
sheet no. 311 . Available from URL:
http://www.who.int/mediacentre/factsheets/fs311/en/in
dex.html
■ Pubmed. K turnhein drugs aging 1998 Nov;13(5):357-79
Available from url:
https://pubmed.ncbi.nlm.nih.gov/9829164/
■ Klaus Turnhein ,Drugs & aging 13 (5), 357-379, 1998
■ Baber N, Pritchard D. Dose estimation for children. British
Journal of Clinical Pharmacology.

39. Thank you.