Читать книгу Clinical Pharmacology and Therapeutics - Группа авторов - Страница 39

There are various reasons why a prescribed dose of drug leads to a different plasma drug concentration and therefore clinical effect. These include:

 Individual differences in absorption, first‐pass metabolism, volume of distribution and clearance

 Altered pharmacokinetics because of gastrointestinal, hepatic or renal disease

 Drug interactions

 Poor adherence to therapy

For most drugs there is an accepted ‘target’ range, i.e. a range of concentrations below which the drug is usually ineffective and above which it is usually toxic. In order to maintain drug concentrations within this range, knowledge about factors that influence the relationships between drug dose and blood concentration is used to design dosage regimens. Dosage adjustments based on age, renal function, hepatic function or other drug therapies are often recommended, especially for drugs with a narrow therapeutic index. For example, the initial dose of gentamicin, a renally cleared antibiotic, is based on the patient's renal function. As a consequence of an interaction that increases digoxin concentrations, the dose of digoxin is usually halved when amiodarone is added to a patient's therapy.