Pharmacokinetics: Prescribing for Paediatric Patients

Factors Affecting Drug Disposition in Children

Children and particularly neonates, differ remarkably from adults in their response     to medications .Special care is required in ensuring that the drug prescribed is appropriate and that the correct dosage is given, especially in the neonatal period (0 – 28 days) of life. 

Oral Absorption:

• Variable gastric and intestinal transit time: In young infants, gastric emptying time is prolonged. It approaches adult values at around 6 months of age. In older infants, intestinal hurry may occur.
• Increased gastric PH:  Gastric acid output does not reach adult values until baby is two years.
• Other factors:  Gastrointestinal contents, posture, disease states and therapeutic interventions (such as drug therapy) can also affect the absorption process.

Distribution:

• Increased total body water: As a percentage of total body weight, the total body water and extracellular fluid volume decrease with increasing age. Neonates require higher doses of water- soluble drugs, on an mg/kg basis than adults.
• Decreased plasma protein building: plasma protein building in neonates is reduced as a result of low levels of albumin and globulins and an altered binding capacity. High circulating bilirubin levels in neonates may displace drugs from albumin.

Metabolism

• Enzyme systems mature at different times and may be absent at birth, or present in considerably reduced amounts.
• For some drugs, altered metabolic pathways may exist.
• Metabolic rate increases dramatically in children and is often greater than adults. Compared with adults, children may require more frequent dosing or higher doses on an mg/kg basis.

Excretion:

Until 6-8 months of age, complete maturation of renal function is not reached.

Route of Administration and Drug Regimens

1. Compliance in children is influenced by the formulation, taste, appearance and ease of administration of the preparation.
2. Prescribed regimens should be tailored to the child’s daily routine and where possible, treatment goals should be set in collaboration with the child.
3. Where possible, the use of products which avoid the need for administration during school hours should be considered (e.g.; drugs with long half –lives or modified – release drugs). 
4. Most schools will request written permission from parents / guardians to administer the medicine, or may ask parents to return to school to give the medicine themselves to their child.
5. Whenever possible, painful intramuscular ( IM) injections should be AVOIDED in children.

Prescription Writing

• Inclusion of age is a legal requirement in the case of prescription. It is preferable to state the age, the strengths of capsules or tablets for all prescriptions for children.
• Liquid preparations are suitable for children; they may contain sugar which encourages dental decay. Sugar – free medicines are therefore preferred for long term treatment. Many children may be able to swallow tablets or capsules and may prefer solid dosage form. Involving the children and their parents in choosing the formulation is helpful.
• Use an oral syringe for liquid oral preparation where the dose ordered is less than 5ml.
• Parents should be advised not to add medicines to the infants feed, since the drug may interact with the milk or other liquid in it; moreover, the ingested dosage may be reduced if the child fails to drink all the contents.

Dosages

When considering drug use in children, the following age groups should be used:

1. Preterm ( born before 37 weeks)
2. Neonates ( birth to 1 month)
3. Infant ( 1 month to 12 months)
4. Child ( 1 to 12 years)
5. Adolescent ( 12 to 18 years )

 Dose Calculation

1. Children doses may be calculated from adult doses by using age, body weight or body surface area, or by a combination of these factors. The most reliable methods are those based on body surface area.
2. Body weight may be used to calculate doses expressed in mg/kg. Young children may require a higher dose per kg than adults due to their higher metabolic rates.
3. Calculation by body weight in the overweight child may result in much higher doses being administered than needed. In such case, the dose should be calculated from an ideal weight, related to height and age.
4. Body surface area estimates are more accurate for paediatric doses than body weight since many physiological phenomena correlate better to body surface area.

Adverse Drug Reactions (ADRs):

ADR profiles in children may differ from those seen in adults. Doctors and pharmacists must report suspected ADRS to NAFDAC(pharmacovigilance unit); identification and reporting of adrs in paediatrics is particularly important because:

1. Drugs are not extensively tested in children 
2. The action of the drug and its pharmacokinetics in children (especially in the very young) may be very different from that in adults.
3. Suitable formulations may not be available to allow precise dosing in children.
4. Many drugs are not specifically licensed for use in children and are used “ off – label”

Safety in the Home

Patients must be told to keep all medicines out of the reach of children. All solid dosage forms and all oral and external liquid preparations must be dispensed in a “child – resistant” container, unless:

1. The parent will have problem in opening a child – resistant container
2. No suitable child – resistant container exists for a particular liquid    preparation.