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 Rationality of pharmacokinetic study in special population

 Pediatric pharmacokinetic study
 Geriatric pharmacokinetic study
 Pharmacokinetic studies in pregnant and lactating women
 Summary
 Conclusion
 References

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RATIONALITY OF SPECIAL POPULATION
STUDY-
 Pharmacokinetic data has helped to distinguish

difference in drug disposition & drug sensitivity in

pediatric, geriatric & pregnant or lactating women as

compared to adult thereby leading to establishment

of specific dosage regimen.

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 PEDIATRIC PHARMACOKINETICS

 Premature- less than 36

weeks gestational age.
 Neonates-less than 30
days.
 Infants- 1 month until 1 yr
of age.
 Child- 1yr until 12yrs of
age.
 Adolescent- 12yrs -18yrs

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Pediatric pharmacology- what’s
unique?
 Continuous development from embryo to adolescent.
 “perpetual pharmacological moving target”
 Pharmacokinetic & pharmacodynamic change with
time.
 The most profound differences occurs in the first few
weeks through first year of life.
 Descriptive pharmacology(especially for new drugs) in
pediatric patients is often lacking.

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Hepatic ontogeny:-
 Phase I(oxidative, hydrolysis, reduction,
demethylation)
• Activity low at birth.
• Oxidative metabolism increases rapidly after birth.
• Alcohol dehydrogenase reaches adult levels at 5yrs.
• Activity in young children exceeds adult level.

 Phase II(conjugation, acetylation, methylation)

• Conjugation: glucoronidation decreases at birth and
sulphatation increases at birth.
• Acetylation decreases at birth ,”fast” or “slow”
phenotype by 12-15 months. 8
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GERIATRIC PHARMACOKINETICS

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 GERIATRIC PHARMACOLOGY-
WHAT’S UNIQUE?
 Changes in underlying physiology occurs over time. They
are-

Decreased beta-adrenergic responsiveness & decreased baro

receptor function.

Increased blood pressure with left ventricular hypertrophy.

Decreased body water & increased body fat.

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 Geriatric pharmacology- Effects on
body systems
 Body composition:- decreased total body water , decreased
serum albumin & increased a1-acid glycoprotein.

 Increased sensitivity to depressant drugs- ethanol, anti-

cholinergic drug, anti-psychotic drug.

 CVS :- cardiac output fairly well maintained .

 Delirium & dementia complicates therapy.

 Any pro-arryhthmic side effects can be accentuated.

 Responsiveness & appropriate reflex effects are diminished.
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Pharmacokinetics in Pregnant and
lactating women

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Pharmacology of pregnant/lactating women:
What’s unique?

 Drug use during pregnancy and lactation requires

special consideration because both the mother and the
child are affected.
 Few drugs are considered safe, and drug use is
generally contraindicated.
 Many pregnant or lactating women take drugs for
acute or chronic disorders or habitual use of alcohol
and tobacco.

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Principles of Therapy: Pregnancy

Give medications only when clearly indicated, weighing

benefits to the mother against the risks to the fetus.

Any drugs used during pregnancy should be given in the

lowest effective doses & for the shortest effective time.

The choice of drug should be based on the stage of

pregnancy and drug information.

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Physiological changes in pregnant women:
 50% increase in plasma volume & total body weight.

 Increased weight(app 14kgs) & body fat.

 Decreased serum albumin.

 Rate of albumin production is increased. However, serum level falls

because of plasma volume expansion.

 Many plasma-protein binding sites are occupies by hormones that

increases during pregnancy.

 Increased renal blood flow and GFR.

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 Pharmacokinetics Changes in pregnant women:

 water-soluble drugs are distributed more than in non-pregnant state.

 Drug dosage requirements may increase.
 Fat soluble drugs are distributed more widely.
 Drugs distributed to fatty tissues tend to linger in body.
 More free drug is available for therapeutic or adverse effects on the mother & for
placental transfer.
 Increased excretion of drugs especially those excreted primarily unchanged in
urine.
 In late pregnancy, the increased size of the uterus decreases renal blood flow in
supine position which results in decreased excretion of renally excreted drugs.

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 Principles of therapy: lactation

Most systemic drugs taken by the mother reach the infant in

breast milk.

For some, amount of drug is For contraindicated

too small. Give medication
drugs, mother should
only when clearly
For other effects are unknown stop drug or stop
indicated.
or potentially adverse. breast feeding.

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Fetal Therapeutics:-
Prenatal Beta -methasone to promote surfactant
production in preterm infants.

Digoxin for fetal tachycardia or heart failure.

Levo-thyroxine for hypothyroidism.

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 Summary:-
 Pediatric- children & infants, specially neonates, have different
pharmacokinetic parameters than adults.
 Appropriate drug therapy can’t be assumed to be identical to adults. So,
each drugs requires clinical studies before being used in children as each
agent is unique.

 Geriatric- normal homeostatic mechanisms are blunted, sometimes

produces inappropriate responses.
 Metabolism & renal excretion/elimination are most often impacted.

 Pregnant & lactating women-increased weight (app 14kg),fat soluble drugs

are distributed more widely. Drugs distributed to fatty tissues tends to
linger in body because of slow release from storage sites.
 Decreased level of serum albumin ,so more drugs are available for
therapeutic or adverse effects on the mother and for placenta.
 Conclusion:-
 It can be concluded from pharmacokinetic studies of special population
that-
 For pediatric patients, compliances may be difficult to achieve due to many
factors like patients is so young to have medicine of their own, so parents
inability to follow instructions & measuring errors etc. has to be minimized
& pediatric dose should never exceed the adult dose.

 For geriatric patients, pharmacokinetic parameter like the age related

changes in renal clearance is the most consistent & predictable change. To
minimize such problems, avoid prescribing before a diagnosis is made &
start low dose based on tolerance & response. Self-medication & multiple
medication should be avoided.

 For pregnant & lactating women, medication should only be given when
clearly indicated and should be based on stage of pregnancy, because most
drugs taken by the mother reaches infant by breast milk. Drugs may cause
teratogenicity & other adverse effects.
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 REFERENCES :-
1. www.slideshare.net, pharmacokinetics in special
populations by- P.C.CAMPO.
2. Drugs used in pregnancyandlactation-pptx- by
M.H.FARJOO, Shahid sehesti university of Medical
Science.
3. Age-kinetics- Age & pharmacokinetics,Edition-
2006,M.E.Blair Holbein.
4. www.medchap.in-pediatric pharmacology.
5. www.researchgate.net,special population kinetic by Itali
Poggesi, Janssen research & development.
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