• To review the physiologic differences affecting pharmacokinetics in neonates.
• To review basic concepts in making drug choices for the neonatal canine and feline.
• To familiarize practitioners with the most commonly used drugs in neonates.
• To review specific drugs commonly used and avoided in the neonate.
General Key Points
• Neonates are not small dogs or cats, there are major physiologic differences affecting drug use.
• Most published drug dosages have been empirically chosen. Few scientific studies exist.
• Risk/Benefit analysis must be applied to choices.
• Whenever possible, avoid drug use in neonates.
• The neonate's physiologic differences from the adult can greatly alter how drugs are handled by the body.
• The cardiac output is rate dependant in the neonate. The resting output is very near the maximum potential output. Cardiac
reserve is minimal.
• High metabolic rate leads to high oxygen consumption.
• Neonates poorly regulate their body temperature.
• The blood-brain barrier is more highly permeable.
• Neonates have low protein binding of drugs due to reduced albumin.
• High body water content, low body fat. Extracellular fluid volume higher than adult.
• Decreased renal function, reduced renal clearance.
• Immature hepatic enzyme function leads to reduced hepatic clearance.
• Absorption of drugs administered by both oral and parenteral routes may differ from the adult.
• Small muscle mass and reduced vascularity affect the absorption of intramuscularly injected drugs.
• Subcutaneous absorption will vary with age, reduced subcutaneous fat stores leads to more rapid absorption of most substances.
Avoid administering hypertonic solutions subcutaneously. Hypothermia slows absorption.
• Oral absorption is affected by increased intestinal permeability in the early neonatal period. Delayed GIT transit times
will also delay absorption.
• Intraosseous or intraperitoneal administration of drugs may speed absorption. The intratracheal and rectal routes may also
be utilized in emergency situations.
• Neonates have higher percent body water and more fluid in the ECF space. Highly water soluble drugs may have reduced plasma
concentrations. Highly fat soluble drugs may have increased plasma concentrations.
• Plasma protein levels are lower than adult levels and neonatal albumin displays less affinity for binding to drugs. Drugs
which are usually highly protein bound may have increased plasma levels.
• The blood-brain barrier is much more highly permeable in the neonate increasing the risk of toxicity with certain drugs.
• Metabolism of drugs by an immature hepatic enzyme system that has reduced metabolic capacity is slower than that in adults.
Pro-drugs may have reduced efficiency due to delay in formation of the active metabolite.
• Renal mechanisms of elimination are immature and rates of elimination are slower than in adults. Use caution with highly
water soluble drugs that have potential for toxicity.
Types of drugs commonly used in neonates
• It is generally recommended to avoid the oral route of administration for antibiotics in critically ill neonates.
• Choices should be based on bacterial species involved. If possible cultures should be obtained prior to beginning therapy.
• Every antibiotic carries some type of risk associated with its use, but none are absolutely contraindicated.
• Beta-lactams are usually considered the safest and best first choice. Chloramphenicol use is controversial due to safety
issues involving blood dyscrasias associated with its use. Tetracyclines can cause not only acute toxicity, but their calcium
chelating properties may lead to tooth and bone development issues. Aminoglycosides have oto- and nephro- toxicity capabilities
leading to recommendations of careful therapeutic drug monitoring by Plumb and others.The fluroquinolone antibiotics are still
considered controversial due to cartilage problems reported in the rapid growth phase. In neonates however, many consider
their risks far outweighed by the potential benefits.