The document discusses important considerations for pediatric drug handling. It covers pharmacokinetic parameters like absorption, distribution, metabolism, and excretion that differ in children compared to adults due to developmental changes. The document emphasizes the need for pediatric clinical trials to determine appropriate drug dosages, formulations, and administration methods for children of different ages. Monitoring growth, vital signs, and laboratory parameters is also important for safe drug therapy in children.

1. Presented By:
Nirav Vachhani
M.Pharm (Sem III)
Guided By:
Mr. Pinakin Jadadv
Assistant Professor
Deparment of Pharmacology,
S. J. Thakkar Pharmacy Collrge, Rajkot.

2. Presented By:
Nirav Vachhani
M.Pharm (Sem III)
Guided By:
Mr. Pinakin Jadadv
Assistant Professor
Deparment of Pharmacology,
S. J. Thakkar Pharmacy Collrge, Rajkot.

3. • Introduction
• Importance Of Pediatric Drug Handling
• The Normal Child
 Pharmacokinetic of Children
 A, D, M, E
 Monitoring Parameters
 Drug Therapy in Children
 Dose Calculation
Contents
 Appropriate Dosage form and route
 Diseases condition
 Adverse reaction in Therapy
 Counseling
• Summary
• References
3

4. Introduction
• Pediatric means..
• As per ICH (2000) ,Childhood is divided in..
Age:- 1- 24 Age:- 12-18 years
months (Adolescents)
(Infants)
Age:- Up to 28 Age:- 2- 11
days years
(Neonate) (Children)
• Topics will cover information on P’kinetic parameters,
Choice of Drug dosage and its form and aspects on
adverse reaction.
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5. Importance of drug handling:
 Lack of data on important pharmacokinetic and
pharmacodynamic differences has led to several terrible
situations in pediatric care.
 One is an ethical issue, the inability to obtain true
informed consent.
 The second obstacle is inherent to children; they grow
and change rapidly.
 Infancy and childhood is rapid stage of development and
various organs, enzymes and body systems that handle
drugs and their dosage are different in time. So, Drug
studies must be performed on children at each stage of
their development to determine appropriate usage.
 Highly Critical aspects in child treatment are
 P’kinetic parameters
 Method of drug administration
 Dose & dosage forms
5

6. The Normal Child:
• Growth and development are important indicators of a
child’s general well-being and pediatric practitioners
should be aware of the normal development milestones
in childhood.
• The World Health Organization (WHO) has publised
the widely used growth charts.
• Three important tools in developmental assessment.
– Height
– Weight
– Head circumference
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7. 7

8. • In addition to the above, assessments of hearing,
vision, motor development and speech are undertaken
at the child health clinics.
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9. Pharmacokinetics:
• There is high importance of clinical pharmacokinetics
in optimization of drug therapy.
• Drugs that are safe and effective in one group of
pediatric patients may be ineffective or toxic in
another, so an understanding of variability in drug
disposition is essential if children are to receive
rational and appropriate drug therapy.
A DISTRIBUTION
M EXCRETION
ABSORBTION
D METABOLISM
E
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10. A • Two factors affecting the absorption of drugs
from the G.I. tract are pH-dependent passive
diffusion and gastric emptying time. Other is G.I.
tract enzyme activity.
• Premature Infants- Elevated pH (More
PH than Infant)
• Infant- Range from 6-8
• Infants/Noenate:- Prolonged gastric
Gastric
emptying time. But lower peristaltic
Emptying movement than older child and adults.
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11. A • In premature infants, higher serum concentrations of
acid-labile drugs—such as penicillin, ampicillin and
nafcillin—and lower serum concentrations of a weak
acid such as phenobarbital can be explained by higher
gastric pH.
• Gastric emptying time:-
– Gastric emptying time is delayed in infants and
reaches adult levels by 6 to 8 months of age.
– Drugs that are absorbed primarily in the stomach may
be absorbed more completely than anticipated. In the
case of drugs absorbed in the small intestine,
therapeutic effect may be delayed. Peristalsis in the
neonate is irregular and may be slow.
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12. A • Gastrointestinal enzyme activities:-
– It is lower in the newborn than in the adult.
Activities of amylase and lipase, beta-
glucuronidase, and glutathione peroxidase
enzymes are low in infants up to 4 months of age.
Neonates also have low concentrations of bile
acids and lipase, which may decrease the
absorption of lipid-soluble drugs.
• Absorption from Intramuscular route:-
– less predictable absorption in infant
– Examples like Diazepam Rapid Absorption ,
Phenobarbital Poor absorption
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13. A • Absorption from Skin :-
– Percutaneous absorption may be increased in
neonate because of an underdeveloped epidermal
barrier (stratum corneum) and increased skin
hydration.
• Absorption from Rectal route :-
– The rectal route of administration can be useful
in infants or children who are unable to take oral
medication.
– The mechanism of rectal route absorption is
probably similar to that of the upper part of GI
tract, despite differences in pH, surface area
and fluid content.
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14. D • Drug distribution is determined by
– Physicochemical properties of the drug
itself (pKa, molecular weight, partition
coefficient,etc…)
– Physiologic factors specific to the patient.
• So, variable aspect is the physiologic
functions such as
– Total Body Water
– Plasma Protein binding of drug
– Volume of Distribution
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15. D
• 94% in the fetus, 85% in premature
Total Body
infants, 78% in full-term infants, and
Water 60% in adults.
Plasma • Less in Newborn and infants
Protein • Reasons
Binding • Examples
• The decrease in plasma protein binding
VD of drugs can increase their apparent
volumes of distribution
15

16. M • Drug metabolism is substantially slower in
infants compared with older children and
adults.
• Less maturation of various pathways of
metabolism within a infant.
• E.g. :- sulfation pathway is well developed but
the glucuronidation pathway is undeveloped in
infants.
• The cause of the tragic chloramphenicol-
induced gray baby syndrome in newborn
infants is a decreased metabolism of
chloramphenicol by glucuronyl transferases to
the inactive glucuronide metabolite.
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17. M • Because of decreased metabolism, doses of
such drugs as theophylline, phenobarbital,
phenytoin, and diazepam should be decreased
in premature infants.
• Particular Microsomal enzymes such as
CYP2C9, CYP2C19, CYP1A2 are variant in
their function.
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18. E • The processes of glomerular filtration, tubular
secretion, and tubular reabsorption determine
the efficiency of renal excretion. These
processes may take several weeks to 1 year
after birth to develop fully.
• Glomerular filtration rate is about 2–4 mL/min
per 1.73 m2 in term infants.
• In infants, if possible then avoid
Chloramphenicol and Amino glycoside, because
their metabolites are accumulated due to
immature function of kidney. Especially
Cloramphenicol metabolites are highly
accumulated due to less developed
glucuronidation pathway, which convert the
cholamphenicol in highly water soluble moiety.
18

19. Monitoring parameters
• Pediatric vital signs, Biochemical and
Hematology parameters change throughout
childhood.
• It gives idea about therapy management in
prolonged treatment.
VITAL SIGNS
Parameters Age (2-5 years) Age (5-12) years
Heart rates 100-120 80-100
(beats/ min)
Systolic Blood 80-90 90-110
pressure (mmHg)
Respiratory rates 25-30 16-25
(beats/ min)
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20. Biochemical Parameters
Parameters Age (2-12 Age (>18 years)
years)
Albumin (g/L) 30-50 35-55
Bilirubin <15 <17
(microM/L)
Creatinine(micro 30-80 50-120
M/L)
Hemoglobin(g/dL) 11-14 13.5-18(male)
12-16(female)
WBC (*109/L) 5-14 3.5-11
20

21. Drug therapy in pediatrics
1. Dose calculation
2. Choice of dosage form
3. Disease Condition
4. Adverse reaction
5. Counseling
21

22. 1. Dose calculation :-
• Height and Wt growth are rapidly changing
factors in childhood, which also influence
significantly some p’kinetic parameters. So, this
factors should be considered during therapy. So
dose calculation is needed.
• Doses should be obtained from pediatric book
for children.. For example, In india IAP-Drug
formulary is reliable source for pediatric
practice and their important drugs.
• For many years, pediatric dosage calculations
used pediatric formulas such as Fried’s rule,
Young’s rule, and Clark’s rule. These formulas
are based on the weight of the child in pounds,
or on the age of the child in months, and the
normal adult dose of a specific drug.
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23. 23

24. 2. Choice of Dosage form :-
Oral Route
• Tablets are less convenient
• Liquid preparation are easy to administer in
accurate dose and to form in desirable dose
by dilution
Parenteral Route:-
• Site of Access
• Safety from fluid overload
• Aware about Excipients
• Other routes like….
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25. • Dose regimrn selection :-
Factors to be considered when selecting a
drug regimen or rout of administration for a
pediatric patient are…
– Age/Weight/Surface area
– Assess the appropriate dose
– Assess the most appropriate interval
– Assess the route of administration
– Consider the expected response and
monitoring parameters
– Interactions
– Legal consideration
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26. 3. Diseases condition :-
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27. Liver disease :-
• Drugs with a high hepatic extraction ratio (>0.7;
such drugs include morphine, meperidine,
lidocaine, and propranolol).
• Clearance of these drugs is affected by hepatic
blood flow. A decreased hepatic blood flow in the
presence of such disease states as cirrhosis and
congestive heart failure is expected to decrease
the clearance of drugs with high extraction
ratios.
• Theophylline clearance may decrease by 45% in a
child with acute viral hepatitis.
• Because of a lack of specific data on dosage
adjustment in liver disease, drug therapy should
be monitored closely in pediatric patients to avoid
potential toxicity from excessive doses.
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28. Renal disease :-
• Renal failure decreases the dosage requirement of
drugs eliminated by the kidney. Once again, because
of limited studies, dosage adjustments in pediatric
patients are based largely on data obtained in adults.
• Serum drug concentrations should be monitored for
drugs with narrow therapeutic index and eliminated
largely by the kidney (e.g., aminoglycosides and
vancomycin) to optimize therapy in pediatric patients
with renal dysfunction.
• For drugs with wide therapeutic ranges (e.g.,
penicillins and cephalosporins), dosage adjustment
may be necessary only in moderate to severe renal
failure.
• Renal clearance or rate of elimination is directly
proportional to the glomerular filtration rate, as
measured by endogenous renal creatinine clearance.
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29. Cystic Fibrosis:-
• Drug therapy in pediatric patients with cystic
fibrosis has been reviewed. For unknown reasons,
these patients require increased doses of certain
drugs.
• Studies have reported a higher clearance of such
drugs as gentamicin, tobramycin, netilmicin,
amikacin, dicloxacillin, cloxacillin, azlocillin,
piperacillin, and theophylline.
• Reason : Variations in hepatic metabolic activity
or in phenotypic distribution of metabolic
polymorphisms may explain some pharmacokinetic
differences in CF.
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30. 4. Adverse reaction in therapy :-
• Mechanism is not cleared in adverse effect of
many drugs in child. But it may be due to
immature p’kinetic parameters and some
medication errors.
• Some well known adverse effect
• Tetracycline  Teeth brown coloration
• Corticosteroids  Growth suppression in
Prepubertal child.
• Paradoxical hyperactivity in child with
phenobarbital treatment
• Aspirin treatment  Reye’s syndrom
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31. • Medication errors are also considered as an
important cause of ADRs and should always
be considered as a possible causative factor
in any unexplained situation.
• The incidence of medication errors and the
risk of serious errors occurring in children
are significantly greater than in adults.
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32. 5. Counseling adherence and concordance
• Parents are often responsible for the
administration of medicines to their children and
therefore the concordance and adherence of
both parties must be considered.
• Non-adherence may be caused by several
factors such as patient resistance to taking the
medicine, complicated dosage regimens,
misunderstanding of instructions and apparent
ineffectiveness or side effects of treatment.
• Several general principles should be considered
in an attempt to improve adherence.
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33. • Attention should be given to the formulation,
taste, appearance and ease of administration of
treatment.
• The regimen should be simple and tailored to the
child’s walking day.
• Many health professionals often counsel the
parents only, rather than involving the child in
the counseling process.
• Where possible, treatment goals should be set in
collaboration with the child.
• Studies have shown that parents consider the 8-
10 year age groups the most appropriate at
which to start including the child in the
counseling process.
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34. • Main key Points covered in topic…..
– Children are not small adults
– Patient details such as age, weight and surface
area need to be ensure appropriate dosing
– Weight and surface area may change
significantly in a relatively short time period
– Pharmacokinetic changes in childhood are
important and have a significant influence on
drug handling and need to considered when
Summary
choosing an appropriate dosing regimen for a
child
– The use of an unlicensed medicine in children is
not illegal although it must be ensured that the
choice of drug and dose is appropriate.
34

35. 1) Parthasarthi G, Hausen KN and Nahata MC. Pediatric
pharmacy practice. In parthasarthi G, Hausen KN and
Nahata MC edited A textbook of clinical pharmacy
practice, 1st Edition. Universities Press Private Ltd,
2008; 160-189.
2) EMEA 2005 Reflection paper: formulations of choice
for the paediatric population. European Medicines
Evaluation Agency, London. Available online at:
www.eniea.eu.int/pdfs/human/peg/19481005en.pdf
References
3) International Committee on Harmonization 2000 Note
for guidance on clinical investigation of medicinal
products in the paediatric population. European Agency
for the Evaluation of Medicinal Products, London
4) McIntyre J. Conroy S. Avery A et at 2000 Unlicensed
and off label prescribing of drugs in general practice.
Archives of Disease in Childhood 83: 498-501
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36. 5) National Institute for Clinical Excellence 2000 Guidance
on the use of inhaler systems (devices) in children under
the age of 5 years with chronic asthma. Technology
Appraisal No 10. National Institute for Clinical
Excellence. London
6) National Institute for Clinical Excellence 2002 Asthma-
inhaler devices for older children. Technology Appraisal
No 38. National Institute for Clinical Excellence, London
7) Scott E, Swanton J, McElnay Jet al 1995 Pharmacists
and child health. Centre for Pharmacy Postgraduate
Education/HMSO, London
8) Turners. Longworth A, Nunn A J et al 1998 Unlicensed
and off-label drug use in paediatric wards: prospective
study. British Medical Journal 316:343-345
9) Yeung S C, Ensom M H 2000 Phenytoin and enteral
feedings: does evidence support an interaction? Annals
of Pharmacotherapy 3(7-8): 896-905
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