Pharmacokinetics in Special Populations (Geriatric, Pediatric, Pregnant)

The very young, the elderly, and pregnant people each have physiology that differs systematically from a typical adult, so the same dose can produce markedly different drug exposure. In children, organ maturation and the developmental rise of metabolizing enzymes (ontogeny) shape disposition; in older adults, declining organ function and changing body composition reduce clearance and alter distribution; in pregnancy, large physiological changes shift absorption, distribution, metabolism, and elimination.

Definition

Special-population pharmacokinetics is the study of how the physiology of distinct life stages - childhood, old age, and pregnancy - systematically alters the absorption, distribution, metabolism, and elimination of drugs, producing exposures that differ from those in a typical non-pregnant adult.

Scope

This topic covers the life-stage physiology that drives pharmacokinetic variability: developmental ontogeny of enzymes and organ function in infants and children; the effects of aging on hepatic and renal clearance and body composition; and the physiological adaptations of pregnancy that change drug disposition. It is a reference and educational topic and provides no dosing guidance for any of these groups.

Core questions

• How does enzyme and organ ontogeny change drug disposition in infants and children?
• How does aging alter hepatic and renal clearance and body composition?
• Which physiological changes of pregnancy reshape pharmacokinetics?
• Why can the same dose give very different exposures across life stages?

Key concepts

• Developmental pharmacology (ontogeny)
• Enzyme maturation in infancy
• Age-related decline in renal and hepatic clearance
• Changes in body composition and water content
• Plasma protein binding across life stages
• Physiological changes of pregnancy
• Inter-individual and life-stage variability

Mechanisms

In children, the activities of metabolizing enzymes and the functions of the kidney and liver mature over the first years of life, so neonates and infants can handle drugs very differently from older children and adults, and disposition changes with developmental age rather than weight alone (Kearns et al., 2003). In older adults, glomerular filtration and hepatic blood flow tend to decline, lean body mass and total body water fall while fat fraction rises, and plasma protein levels may change, together reducing clearance and altering the volume of distribution (Klotz, 2009). In pregnancy, increases in plasma volume, cardiac output, glomerular filtration, and the hormonally driven activity of certain metabolizing enzymes and transporters shift absorption, distribution, metabolism, and elimination, so exposure of many drugs changes over the course of gestation (Isoherranen & Thummel, 2013).

Clinical relevance

Because life stage is one of the strongest sources of pharmacokinetic variability, special populations are a central concern of evidence appraisal and of regulatory requirements for studying drugs in children, older adults, and pregnancy. This entry explains the underlying physiology for reference and education; it describes how disposition changes and is not a source of dosing or treatment advice for any population.

Evidence & guidelines

The mechanistic picture rests on developmental-, geriatric-, and pregnancy-pharmacology reviews. Regulatory authorities maintain guidance on conducting pediatric, geriatric, and pregnancy pharmacokinetic studies and on extrapolating adult data, reflecting the recognised disposition differences in these groups.

History

Pediatric drug disasters of the mid-twentieth century underscored that children are not small adults, spurring the field of developmental pharmacology consolidated by Kearns and colleagues. Parallel work mapped the effects of aging on drug handling, and later research characterised the substantial pharmacokinetic changes of pregnancy, establishing all three as distinct special populations.

Key figures

• Gregory L. Kearns
• Ulrich Klotz
• Nina Isoherranen
• Kenneth E. Thummel

Seminal works

• kearns-2003
• klotz-2009
• isoherranen-thummel-2013

Frequently asked questions

Why are children not simply treated as small adults in pharmacokinetics?

Their metabolizing enzymes and organ functions mature over time, so drug handling depends on developmental stage, not just body size, and disposition can differ substantially from that of adults.

How does pregnancy change drug pharmacokinetics?

Pregnancy raises plasma volume, cardiac output, and kidney filtration and alters the activity of some metabolizing enzymes, so the absorption, distribution, metabolism, and elimination of many drugs shift across gestation.