Therapeutic drug level

First described in 1926 by Perrin [16], the theory was greatly expanded by Weber [17], who developed the first instrumentation for the measurement of FP. Dandliker [18] expanded FP into biological systems such as antigen-antibody reactions and hormone-receptor interactions. Jolley [19] developed FP into a commercial system for monitoring of therapeutic drug levels and the detection of drugs of abuse in human body fluids. 

Jolley, M.E., Fluorescence polarization immunoassay for the determination of therapeutic drug levels in human plasma, ]. Anal. Toxicol., 5, 236,1981. 

The development of biosensors is expected to benefit monitoring therapeutic drug levels, office testing, and implantable devices because of the advantages of cost-saving automation and improved data handling... 

Drug monitoring tends to be of two types 1) assays for specific therapeutic drug levels, closely related analogs, and preparation enhancers and 2) rapid, broad screening for the presence and overdosage detection of drugs of abuse. 

FIGURE 23.8 Effect of age-related clearance of theophylline on the dose of sustained-release theophylline required to maintain a therapeutic drug level (range 10-20 pg/mL) in males (solid bars) and females (open bars) across a broad age range. (Reproduced wdth permission from Milavetz G et ai] Pediatr 1986 109 351-4.)... 

Table 3 Free Fracrions of Drug Enantiomers in Human Plasma at Therapeutic Drug Levels...

S2I6 Parker, D.R., McCall, J., Wise, J., St. Germain, E. and Aitken, G. (1988). Preliminary experience using a prototype semiautomated Seralyzer III to measure therapeutic drug levels. J. Clin. Immunoassay II, 50, Abstr. 10. 

Early signs of tricyclic antidepressant toxicity are due to anticholinergic effects and include tachycardia, mydriasis, dry mouth, low-grade fever, diminished bowel sounds, CNS excitation, and delirium. More serious toxicity is manifested by coma, respiratory depression, seizures, and cardiovascular toxicity including conduction disturbances, hypotension, ventricular arrhythmias, and asystole. Seizures cause hyperthermia, rhabdomyolysis, and metabolic acidosis. Clinical deterioration can be rapid and catastrophic in patients with tricyclic antidepressant overdose. Death most often occurs due to dysrhythmia and circulatory collapse. The typical therapeutic dose of a tricyclic antidepressant is 2-4 mg kg day Doses of 15-20 mg kg are potentially lethal. Therapeutic drug levels for most tricyclic antidepressants range from 100 to... 

Monitor therapeutic drug levels (120-250 ng/ml) toxic greater than 500 ng/ml. 

Because of the very extensive barrier properties of the stratum corneum, it is often necessary to increase the intrinsic rate of dermal or transdermal drug delivery to achieve the required therapeutic drug levels. In these instances, skin penetration and permeation enhancement... 

This medication should be taken at the same time every day to maintain a therapeutic drug level. 

The rationale behind controlled or sustained release has always been the need for a therapeutic drug level that is sufficient without the overdose level that is generally found with injection or other forms of bolus medicant delivery. Oftentimes, there are undesirable side effects associated with bolus drug delivery and, in the case of certain drug therapies, a second drug must be administered to prevent side effects such as nausea. In theory, a properly designed controlled delivery device should overcome or minimize problems associated with pulsed drug delivery. 

A more accurate drug dosage adjustment is recommended for agents that have a narrow therapeutic index when available, measurement of therapeutic drug levels may optimize therapeutic regimens hypoalbuminemia may influence the interpretation of drug concentrations... 

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