PHC5005 Chap.10 Pharmacokinetics in Special Populations
Pharmacokinetics in Special Populations
Why standard doses fail at the edges
This lecture applies every earlier pharmacokinetic idea to five groups whose physiology differs from the adult reference: pregnant women, lactating mothers, children, older adults and people with obesity.
Its intended outcomes are to explain how those differences change absorption, distribution, metabolism and excretion, to adjust doses for developmental stage, pregnancy or obesity, to choose drugs with suitable safety profiles, to identify contraindicated drugs, and to monitor therapy with drug levels and dose changes.
Pregnancy
Most drugs cross the placenta.
Small and lipophilic molecules cross easily, highly protein-bound ones less so, and some are metabolised by the placenta itself. A teratogen must produce a characteristic pattern of malformations, act at a specific developmental stage and show dose dependence; organogenesis, weeks 3 to 8, is the critical period. The FDA letter categories grade the evidence from A to X.
Pregnancy also changes kinetics: vomiting and slow gastric emptying alter absorption, plasma volume rises and albumin falls, hepatic enzyme activity shifts and filtration rises.
The safe-prescribing rules are established drugs, the smallest dose that works for the briefest period, and monitoring of fetal growth.
Lactation
Most drugs appear in milk in amounts too small to matter, but lipophilic, small and basic drugs accumulate, and lithium, atenolol and amiodarone are named exceptions. Transfer depends on maternal plasma level and the milk-to-plasma ratio.
The course lists significant-risk and minimal-risk drugs, and recommends dosing immediately after a feed, avoiding cytotoxic and radioactive agents, and watching the infant for sedation or diarrhoea.
Children and older adults
Children are not scaled-down adults.
Gastric pH, body water, fat, protein binding, liver enzymes and kidney function all differ, so doses are based on weight, age or surface area, with manufacturer paediatric doses preferred and adult doses never exceeded.
In older adults absorption changes little, but more fat and less water prolong lipophilic drugs, Phase I metabolism declines while Phase II is preserved, and falling renal function lets digoxin and aminoglycosides accumulate. The advice is to start low, titrate, prefer short half-lives and inactive metabolites, and watch for interactions.
Obesity
In obesity the key question is which weight to dose on.
Lipophilic drugs distribute into the enlarged fat compartment, so loading doses use total body weight; hydrophilic drugs stay in lean body water, so doses use adjusted or lean body weight. Maintenance doses follow clearance, which rises for renally excreted drugs because renal plasma flow and filtration increase.
What this chapter covers
- 01
Placental transfer and the criteria for teratogenicity
- 02
FDA pregnancy risk categories and the critical developmental period
- 03
Pharmacokinetic changes and safe prescribing in pregnancy
- 04
Drug transfer into breast milk and the lactation risk lists
- 05
Paediatric pharmacokinetics and dose calculation rules
- 06
Geriatric pharmacokinetics and drug classes that need caution
- 07
Lipophilic and hydrophilic dosing in obesity with body-weight formulas
Worked example · free
Adjusting for a child's weight
- 2Apply Clark's rule.
- 2State the limits of rule-based scaling.
Key terms
- Teratogen
- An agent that causes abnormalities in fetal development, producing structural or functional defects.
- Organogenesis
- The period of organ formation, weeks 3 to 8 of gestation, when teratogenic exposure matters most.
- Category X
- The FDA pregnancy category for drugs with demonstrated fetal risk, not to be used in anyone pregnant or who could become pregnant.
- Milk-to-Plasma Ratio
- The ratio of drug concentration in breast milk to maternal plasma, which sets the extent of transfer to the infant.
- Young's Rule
- A paediatric dose estimate: adult dose multiplied by age in years divided by age plus 12.
- Clark's Rule
- A paediatric dose estimate: adult dose multiplied by weight in kilograms divided by 70.
- Ideal Body Weight
- A height-based weight used as the starting point for dosing calculations in obesity.
- Adjusted Body Weight
- Ideal body weight plus 0.4 times the excess of total over ideal body weight, used for hydrophilic drugs in obesity.
Pharmacokinetics in Special Populations FAQ
Why is heparin preferred over some anticoagulants in pregnancy?
Heparin is a large molecule that does not cross the placenta, so the fetus is not exposed. Warfarin, by contrast, appears in the teratogen table for every trimester with effects that include nasal hypoplasia, bone and nervous system malformations and bleeding.
Which drugs carry significant risk during breastfeeding?
The course lists chloramphenicol, codeine, ethanol, heroin, iodine, lithium, methadone and phenobarbitone as significant risks, and ampicillin, penicillin, digoxin, isoniazid, propranolol, thyroxine, warfarin and spironolactone as minimal. Cytotoxic and radioactive agents are contraindicated.
Why can't a child's dose simply be scaled down from an adult's?
Children differ in gastric pH and emptying, body water and fat, protein binding, liver enzyme maturity and kidney function. Neonates, for instance, are 70 to 75 per cent water, which changes how water-soluble drugs such as aminoglycosides distribute, so proportional scaling can over- or under-dose.
Which benzodiazepines are safer in older adults and why?
Lorazepam and oxazepam. They are cleared by Phase II conjugation, which is largely preserved with age, whereas diazepam depends on Phase I oxidation, which declines as hepatic blood flow and enzyme activity fall, prolonging its half-life and sedative effects.
Why do obese patients take longer to recover from propofol?
Propofol is lipophilic and redistributes into the enlarged fat stores. That reservoir releases the drug back into the circulation slowly, so the effective volume of distribution is large and recovery after surgery takes longer.
Which body weight is used for dosing drugs in obesity?
It depends on the drug. Loading doses of lipophilic drugs use total body weight because the drug fills the fat compartment. Hydrophilic drugs such as gentamicin use adjusted or lean body weight, since dosing on total weight could cause toxicity from excessive plasma levels.
Exam move
Build a five-row grid, one row per population, with four columns for absorption, distribution, metabolism and excretion, and a fifth for the prescribing rule. Fill it from memory, then check it against the lecture. The empty cells show exactly which population you need to revise.
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