Pharmacokinetics for psychiatrists

Pharmacokinetics describes the action of the body on administered drugs. This contribution illustrates that an understanding of pharmacokinetic principles is important in rational drug prescribing in psychiatry. Examples are presented to underline the clinical relevance of the important aspects of pharmacokinetics, encompassing drug absorption, distribution, phase I and phase II metabolism and excretion. Particular emphasis is placed on drug metabolism in the liver due to the prominence of cytochrome P450 enzymes such as CYP2D6, CYP3A4 and CYP1A2 in the phase I metabolism of psychotropic drugs. The concept of drugs being enzyme substrates, inhibitors (e.g. paroxetine for CYP2D6, fluvoxamine for CYP1A2 and fluoxetine for CYP3A4 and CYP2D6) and inducers (e.g. carmbamazepine with respect to CYP3A4) are discussed and the ramifications of P450 interactions for clinical practice examined. The potential impact of genetic polymorphisms on drug-metabolizing enzyme activity, such as that for CYP2D6, is also considered. In discussing renal excretion of psychotropic drugs, the impact of changes in lithium clearance, either through declining renal function or co-prescription of interacting drugs, is highlighted. This contribution also outlines further key concepts in pharmacokinetics which are relevant to clinical psychiatry – ‘half-life’, ‘steady state’, ‘area under the curve’ and ‘bioavailability’. Finally, of particular importance when prescribing psychotropic drugs to elderly populations, the changes in drug handling that occur with advancing age are discussed.