Merck Manual

Please confirm that you are a health care professional

honeypot link

Pharmacokinetics in Children


Bridgette L. Jones

, MD, MS, University of Missouri, Kansas City, School of Medicine, Children's Mercy, Kansas City, MO

Reviewed/Revised Dec 2022
Topic Resources


Absorption from the gastrointestinal tract is affected by

  • Gastric acid secretion

  • Bile salt formation

  • Gastric emptying time

  • Intestinal motility

  • Bowel length and effective absorptive surface

  • Microbial flora

  • Illness

Reduced gastric acid secretion increases bioavailability of acid-labile drugs (eg, penicillin) and decreases bioavailability of weakly acidic drugs (eg, phenobarbital).

Reduced bile salt formation decreases bioavailability of lipophilic drugs (eg, diazepam).

Reduced gastric emptying and intestinal motility increase the time it takes to reach therapeutic concentrations when enteral drugs are given to infants < 3 months old. Drug-metabolizing enzymes present in the intestines of young infants are another cause of reduced drug absorption. Infants with congenital atretic bowel or surgically removed bowel or who have jejunal feeding tubes may have specific absorptive defects depending on the length of bowel lost or bypassed and the location of the lost segment. How the type of food consumed may alter gastric emptying should also be considered (eg, solid versus liquid).

Alterations in intestinal flora that aid metabolism may also affect absorption in the gut.

Injected drugs are often erratically absorbed because of

  • Variability in their chemical characteristics

  • Differences in absorption by site of injection (intramuscular or subcutaneous)

  • Variability in muscle mass among children

  • Illness (eg, compromised circulatory status)

  • Variability in depth of injection (too deep or too shallow)

Intramuscular injections are generally avoided in children because of pain and the possibility of tissue damage, but, when needed, water-soluble drugs are best because they do not precipitate at the injection site.

Transdermal absorption may be enhanced in neonates and young infants because the stratum corneum is thin and because the ratio of surface area to weight is much greater than for older children and adults. Skin disruptions (eg, abrasions, eczema, burns) increase absorption in children of any age.

Transrectal drug therapy is generally appropriate only for emergencies when an IV route is not available (eg, use of rectal diazepam for status epilepticus). Site of placement of the drug within the rectal cavity may influence absorption because of the difference in venous drainage systems. Young infants may also expel the drug before significant absorption has occurred.

Absorption of inhaled drugs from the lungs (eg, beta-agonists for asthma, pulmonary surfactant for respiratory distress syndrome) may vary less by physiologic parameters and more by reliability of the delivery device and patient or caregiver technique.

Absorption reference


The volume of distribution Volume of distribution After a drug enters the systemic circulation, it is distributed to the body’s tissues. Distribution is generally uneven because of differences in blood perfusion, tissue binding (eg, because... read more of drugs changes in children with aging. These age-related changes are due to changes in body composition (especially the extracellular and total body water spaces) and plasma protein binding.

Higher doses (per kg of body weight) of water-soluble drugs are required in younger children because a higher percentage of their body weight is water (see figure Changes in body composition with growth and aging Changes in body composition with growth and aging Changes in body composition with growth and aging ). Conversely, lower doses are required to avoid toxicity as children grow older because of the decline in water as a percentage of body weight. Additionally, children with obesity Obesity in Adolescents Obesity is now twice as common among adolescents than it was 30 years ago and is one of the most common reasons for visits to adolescent clinics. Although fewer than one third of adults with... read more have been shown to have significantly higher percentages of total body water, body volume, lean body mass, and fat mass compared to children without obesity (1 Distribution reference Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and elimination. There are important age-related variations in pharmacokinetics. Absorption from the gastrointestinal... read more ).

Changes in body composition with growth and aging

Adapted from Puig M: Body composition and growth. In Nutrition in Pediatrics, ed. 2, edited by WA Walker and JB Watkins. Hamilton, Ontario, BC Decker, 1996.

Changes in body composition with growth and aging

Many drugs bind to proteins, primarily albumin, alpha-1 acid glycoprotein, and lipoproteins; protein binding limits distribution of free drug throughout the body. Albumin and total protein concentrations are lower in neonates but approach adult levels by 10 to 12 months. Decreased protein binding in neonates is also due to qualitative differences in binding proteins and to competitive binding by molecules such as bilirubin and free fatty acids, which circulate in higher concentrations in neonates and infants. The net result may be increased free drug concentrations, greater drug availability at receptor sites, and both pharmacologic effects and higher frequency of adverse effects at lower drug concentrations.

Distribution reference

Metabolism and elimination

Drug metabolism and elimination vary with age and depend on the substrate or drug, but most drugs, and most notably phenytoin, barbiturates, analgesics, and cardiac glycosides, have plasma half-lives 2 to 3 times longer in neonates than in adults.

The cytochrome P-450 (CYP450) enzyme system in the small bowel and liver is the most important known system for drug metabolism. CYP450 enzymes inactivate drugs via

  • Oxidation, reduction, and hydrolysis (phase I metabolism)

  • Hydroxylation and conjugation (phase II metabolism)

Phase I metabolism activity is reduced in neonates, increases progressively during the first 6 months of life, exceeds adult rates by the first few years for some drugs, slows during adolescence, and usually attains adult rates by late puberty. However, adult rates of metabolism may be achieved for some drugs (eg, barbiturates, phenytoin) 2 to 4 weeks postnatally. CYP450 activity can also be induced (reducing drug concentrations and effect) or inhibited (augmenting concentrations and effect) by coadministered drugs. These drug interactions may lead to drug toxicity when CYP450 activity is inhibited or to an inadequate drug level when CYP450 activity is induced. Diet may also affect development of CYP450 activity in children (1 Metabolism and elimination reference Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and elimination. There are important age-related variations in pharmacokinetics. Absorption from the gastrointestinal... read more ). Kidneys, lungs, and skin also play a role in the metabolism of some drugs, as do intestinal drug-metabolizing enzymes in neonates.

Phase II metabolism varies considerably by substrate. Maturation of enzymes responsible for bilirubin and acetaminophen conjugation is delayed; enzymes responsible for morphine conjugation are fully mature even in preterm infants.

Drug metabolites are eliminated primarily through bile or the kidneys. Renal elimination depends on

  • Plasma protein binding

  • Renal blood flow

  • Glomerular filtration rate

  • Tubular secretion

All of these factors are altered in the first 2 years of life. Renal plasma flow is low at birth (12 mL/minute) and reaches adult levels of 140 mL/minute by age 1 year. Similarly, glomerular filtration rate is 2 to 4 mL/minute at birth, increases to 8 to 20 mL/minute by 2 to 3 days, and reaches adult levels of 120 mL/minute by 3 to 5 months.

Metabolism and elimination reference

  • 1. Blake JB, Abdel-Rahman SM, Pearce RE, et al: Effect of diet on the development of drug metabolism by cytochrome P-450 enzymes in healthy infants. Pediatr Res 60(6):717–723, 2006. doi: 10.1203/01.pdr.0000245909.74166.00

Drug dosing

Because of the above factors, drug dosing in children < 12 years old is frequently a function of age, body weight, or both. This approach is practical but not ideal. Even within a population of similar age and weight, drug requirements may differ because of maturational differences in absorption, metabolism, and elimination. Thus, when practical, dose adjustments should be based on plasma drug concentration (however, plasma drug concentration may not reflect the drug concentration in the target organ). Unfortunately, these adjustments are not feasible for most drugs. However, in the US, because of the Best Pharmaceuticals for Children Act of 2001 and the Pediatric Research Equity Act of 2003 (both made permanent in 2012 [ 1 Drug dosing reference Pharmacokinetics refers to the processes of drug absorption, distribution, metabolism, and elimination. There are important age-related variations in pharmacokinetics. Absorption from the gastrointestinal... read more ]), more complete pediatric dosing, pharmacokinetic, and safety information is available for over 900 drugs for use in children (see also the U.S. Food and Drug Administration [FDA] 2020 status report).

Physiologically based pharmacokinetic modeling is a mathematical technique that uses known principles of biochemistry and physiology to predict how a drug will be absorbed, distributed, metabolized, and excreted. Results of this modeling can help support decisions on whether, when, and how to conduct a clinical trial and can help improve the safety and efficiency of pediatric clinical trials.

Drug dosing reference

  • 1. Bourgeois FT, Kesselheim AS: Promoting pediatric drug research and labeling—Outcomes of legislation. N Engl J Med 381(9):875–881, 2019. doi: 10.1056/NEJMhle1901265

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Luminal, Sezaby
Diastat, Dizac, Valium, VALTOCO
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
ARYMO ER, Astramorph PF, Avinza, DepoDur, Duramorph PF, Infumorph, Kadian, MITIGO, MORPHABOND, MS Contin, MSIR, Opium Tincture, Oramorph SR, RMS, Roxanol, Roxanol-T
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz!