Pharmacokinetics in Anaesthesia and Adult Intensive Care

The equations below describe a first-order model with a constant elimination-rate constant. They are conceptual relationships, not patient-specific calculations.

C is concentration, expressed as mass per volume or amount per volume; the subscripted C symbol in the exponential equation is the initial concentration in the same dimension; t is time; k is the elimination-rate constant with the dimension reciprocal time; dC/dt is change in concentration per unit time. No rounding is applied.

dC/dt = −kC

C(t) = C₀e^(−kt)

t½ = ln(2)/k

Phenytoin has saturable hepatic metabolism, extensive protein binding, and important interactions. Use concentration-aware therapeutic drug monitoring when a valid assay and clinical question exist, and interpret total versus unbound concentration in the patient’s binding context. Near saturation, elimination may approximate zero-order behaviour, but that term describes the kinetics rather than the management.

A central compartment represents blood and rapidly equilibrating tissues; peripheral compartments represent slower tissue exchange. After an intravenous bolus or infusion change, redistribution between compartments can dominate the early concentration fall, whereas terminal elimination describes a later phase.

Context-sensitive half-time is the time for plasma or central-compartment concentration to fall by one half after an infusion stops. It depends on infusion duration and multicompartment distribution; terminal half-life alone is a poor predictor of awakening after an infusion.

Propofol follows a multicompartment model. Rapid plasma–brain equilibration supports onset, while distribution into slower tissues and tissue stores becomes more important as infusion duration increases.

Thiopental rapidly reaches highly perfused brain tissue and then redistributes to other tissues. Its lipid solubility permits storage in tissue depots and slow release back to plasma; distinguish that depot release from ongoing drug delivery.

Midazolam can accumulate in peripheral tissues during continuous infusion. Infusion duration, patient condition, hepatic blood flow, metabolism, and renal handling of conjugated metabolites all influence recovery.

Fentanyl has multicompartment distribution, accumulates in muscle and fat, and is released slowly back into blood. Redistribution and tissue storage therefore matter after prolonged exposure.

Remifentanil distributes through central and peripheral compartments but is hydrolysed by nonspecific esterases in blood and tissues. During registered use, offset remains rapid and does not progressively lengthen with prolonged administration.

After intravenous ketamine, the early concentration decline reflects redistribution from the central nervous system to slower tissues as well as hepatic conversion to norketamine. Redistribution and metabolism should be considered separately.

Renal dysfunction can alter excretion of a parent medicine or active metabolite and can change protein binding. Establish which moiety is measured and use the product-specific information for renal impairment.

During CRRT, extracorporeal removal depends on the medicine, unbound fraction, distribution, membrane, modality, operating conditions, residual kidney function, and the patient. Reassess exposure and effect without a fixed correction factor.

Age can change distribution, intercompartmental clearance, peak concentration, sensitivity, and recovery. Propofol labelling describes age-related pharmacokinetic differences, so response-guided reassessment is essential.

Obesity may increase midazolam volume of distribution. Separately, conditions that diminish cardiac output and hepatic blood flow may reduce clearance. Interpret each factor separately in the patient’s exposure context.

Hepatic dysfunction and interacting medicines may alter fentanyl transformation or pharmacodynamic effect. Relate perfusion, concomitant depressants, and the observed respiratory response to the fentanyl exposure.

Hypothermia can reduce remifentanil clearance in the specific setting described for hypothermic bypass. The reported direction and magnitude belong to that setting and may differ with other temperatures, patients, or extracorporeal circuits.

Pregnancy is a distinct population boundary for ketamine. Interpret exposure in the context of maternal physiology, indication, concomitant medicines, and pregnancy-specific prescribing information rather than applying one adjustment across pregnancy.

Hypoalbuminaemia and renal or hepatic disease can increase the clinical importance of unbound phenytoin. In these settings, an unbound measurement may be more informative; relate it to symptoms and the clinical question.

Because pregnancy can alter phenytoin protein binding, base serum-level monitoring during pregnancy on the unbound fraction and interpret it with the clinical response.

During ECMO, drug sequestration depends on the molecule, circuit, and time in service. Experimental midazolam data show circuit- and drug-dependent variability that cannot be represented by a single correction factor.