Modern drug analysis in biological fluids suitable for clinical pharmacokinetics

Abstract

Therapeutic drug monitoring can provide valuable information to guide clinicians in achieving optimal treatment with selected therapeutic agents. Large intersubject variations in drug response are common. There are many factors that may cause variability in drug disposition and drug plasma levels using standard dosage regimens: (1) Biometric factors: age, height, weight; (2) Absorption and patient compliance; (3) Distribution, cardiac failure; (4) Elimination: hepatic and/or renal failure; (5) Individual capacity in metabolizing drugs; (6) Drug-drug interactions. All these factors demand dosage adjustments for the individual patient and contribute to the observation that the correlation between drug plasma level and response is much better than that between the total dose and response among a given patient population. Pharmacokinetic-pharmacodynamic studies yield information on the therapeutic plasma concentration range of a drug that should be maintained during therapy to achieve maximum benefits. This leads to the concept of the ‘target level’ of a particular drug in plasma, which is important for the application of clinical pharmacokinetics in drug therapy. There are two ways by which ‘target levels’ can be utilized to optimize the individual drug dosage regimen: first, calculation of the dose based on predictive pharmacokinetic models for the individual patient; and second, inclusion of drug level monitoring to correct the predictive model for unaccountable intersubject variation. Predictive pharmacokinetic models are particularly useful for drugs that are mainly eliminated by renal excretion, since good correlations between clinical kidney function tests and drug clearance have been established. Thus dosage adjustments, based on individual kidney functions, are an integral part of modern drug therapy with drugs like