Pharmacokinetics

Pharmacokinetics

Pharmacokinetics is the description of the time course of a drug in the body, encompassing absorption, distri-bution, metabolism, and excretion. In simplest terms, it can be described as what the body does to the drug. Pharmacokinetic concepts are used during drug devel-opment to determine the optimal formulation of a drug, dose (along with effect data), and dosing frequency. For drugs with a wide therapeutic index (difference be-tween the minimum effective dose and the minimum toxic dose), knowledge of the drug’s pharmacokinetic properties in that individual patient may not be partic-ularly important. For example, nonsteroidal antiinflam-matory drugs, such as ibuprofen, have a wide therapeu-tic index, and thus knowledge of the pharmacokinetic parameters in a given individual is relatively unimpor-tant, since normal doses can vary from 400 to 3200 mg per day with no substantial difference in acute toxicity or effect. However, for drugs with a narrow therapeutic index, knowledge of that drug’s pharmacokinetic profile in an individual patient has paramount importance.

If there is little difference between the minimum effective dose and the toxic dose, slight changes in a drug’s pharmacokinetic profile, or even simply in-terindividual differences, may require dosage adjust-ments to minimize toxicity or maximize efficacy. For ex-ample, the blood concentrations of the antiasthmatic drug theophylline must usually be maintained within the range of 10–20  μg/mL. At concentrations below this, patients may not obtain relief of symptoms, while concentrations above 20  μg/mL can result in serious toxicities, such as seizures, arrhythmias, and even death. Thus, a drug’s pharmacokinetic profile may have im-portant clinical significance beyond its use in drug de-velopment.