Drug concentration measurement

The basic principles outlined above can be applied to the interpretation of clinical drug concentration measurements on the basis of three major pharmacokinetic variables absorption, clearance, and volume of distribution (and the derived variable, half-life) and two pharmacodynamic variables maximum effect attainable in the target tissue and the sensitivity of the tissue to the drug. Diseases may modify all of these parameters, and the ability to predict the effect of disease states on pharmacokinetic parameters is important in properly adjusting dosage in such cases. (See The Target Concentration Strategy.)... 

An accurate dosing history is essential if one is to obtain maximum value from a drug concentration measurement. In fact, if the dosing history is unknown or incomplete, a drug concentration measurement loses all predictive value. 

Therapeutic blood concentrations described in this chapter are based on studies that relate to drug concentrations measured at steady state of patients treated with recommended daily doses of a drug. However, the same dose of a drug can result in considerably different plasma concentrations in different individuals, depending on factors such as diet, lifestyle, comedication, and genetic makeup resulting in altered absorption, distribution, and elimination of drugs. 

Effect of pH on the incorporation of cocaine, benzoylecgonine, and morphine into hair. Caucasian brown hair was exposed to the drug (5 pg/mL) containing a radioactive tracer in 10 mM phosphate buffer at the indicated pH for 1-h, The hair was rinsed three times with water and dried. A 30-min ethanol decontamination was followed by six phosphate decontamination washes. The hair was then digested with sodium hydroxide and the drug concentration measured by scintillation counting. 

Misinterpretation of total drug concentration measurements may occur if albumin concentration is <30 g/L and the drug is > 80% bound to albumin. 

Additional clinical information is often necessary to interpret drug concentration measurements that are... 

Despite these technical advances, adverse reactions still occur frequently with digoxin, phenytoin, and many other drugs for which drug concentration measurements are routinely available. The persistence in contemporary practice of dose-related toxicity with these drugs most likely reflects inadequate understanding of basic pharmacokinetic principles. This is illustrated by the following case history (5) ... 

Many drugs have distribution volumes that exceed expected values for TBW, or are considerably larger than ECF despite extensive binding to plasma proteins. The extensive tissue binding of these drugs increases the apparent distribution volume that is calculated by reference to drug concentrations measured in plasma water. By modifying Equation 3.1 as follows. 

Given the perceived failure of spontaneous reporting systems and the paucity of ADR reports/ some institutions have instituted more active methods of ADR detection to supplement spontaneous reports. Medication order screening has become a common practice in U.S. hospitals. Manual chart reviews and audits and computer programs are used for retrospective/ concurrent/ and prospective medication utilization evaluation. Certain events often prompt an evaluation of a suspected adverse reaction. These include abrupt discontinuation of a medication/ abrupt dosage reduction/ orders for antidotes and emergency medications/ orders for special tests or serum drug concentration measurements/ and abnormal results from laboratory tests and medical procedures. 

Reynolds DJ, Aronson JK. 1993. ABC of monitoring drug therapy. Making the most of plasma drug concentration measurements. Br. Med. J. 306 48-51. 

Cj concentration of the drug in the plasma going into a Hlter Cjd plasma concentration after dialysis Cave average plasma concentration CAVH continuous arteriovenous hemoHltration CAVHD continuous arteriovenous hemodialysis CAVHDF continuous arteriovenous hemodiafiltration Cbo plasma concentration prior to the next dialysis session Cdf concentration of drug in the dialysis fluid equated total phenytoin concentration Cm total drug concentration measured in a patient with altered protein binding... 

Figure 14.4 Visualization of "trough" vancomycin level collected too early. Cp, plasma drug concentration C pk", apparent peak drug concentration Chi, highest drug concentration measured Clo, lowest drug concentration measured Ctr, trough drug concentration.

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