Drug Monitoring Methods
Common Household Chemicals as Urinary Adulterants
People try to beat drug testing by adding adulterants into urine specimens. Several adulterants can cause false-negative results in drug testing by immunoassays. Common adulterants for masking drug testing are as follows and detection of these adulterants by specimen integrity tests is given in Table 2. 5. Golden Seal tea (produces dark urine). AlthoughFPIA is less subjected to interference from adulterants compared to the EMIT, some interference has also been reported with FPIA. Sodium...
Application of gc gcms hplc and hplcms for drug analysis
Although immunoassays are widely used for routine TDM in clinical laboratories, other analytical techniques such as GC, HPLC, GC MS, and HPLC MS are also used for determination of concentrations of various drugs in clinical laboratories Table 2 . These alternative techniques, especially GC MS and HPLC MS, are very sensitive and specific for a chosen analyte whereas immunoassays suffer from multiple problems including interferences from compounds with similar structures, hook effect, and...
Pharmacokinetics and Serum Drug Concentrations
When a drug is given orally, it undergoes several steps in the body and its concentration in serum or whole blood is affected by certain steps. 1. Liberation The release of a drug from the dosage form (tablet, capsule, extended release formulation) 2. Absorption Movement of drug from site of administration (for drugs taken orally) to blood circulation 3. Distribution Movement of a drug from the blood circulation to tissues. This distribution in most cases is reversible. Certain drugs also cross...
Therapeutic drug monitoring of digoxin
Digitalis glycosides have been in use in medicine over 200 years. The main pharmacological effects include a dose-dependent increase in myocardial contractility and a negative chronotropic action. Digitalis also increases the refractory period and decreases impulse velocity in certain myocardial tissue such as the atrioventricular (AV) node . The electrophysiological properties of digitalis are reflected in the ECG by shortening of the QT interval. Both digoxin and digitoxin have narrow...
How To Detect And Remove Antibody Interference
If a test result is unexpected and heterophilic antibody is suspected as the source of interference, several strategies can be adopted for investigation. 1. Dilution linearity study with the specimen is the simplest way to document interference when observed values after dilution deviate significantly from the target values. Figure 1 illustrates the effect of successive dilutions of a HAMA containing sample (spiked with 32 g mL of theophylline but observed value was 59 g mL) compared to a...
Drug metabolism and clearance in neonates children and elderly
In the fetus, CYP3A7 is the major hepatic cytochrome responsible for steroid metabolism. Variably expressed in the fetus, CYP3A5 is also present in significant level in half of the children. However, in adults, CYP3A4 is the major functional hepatic enzyme responsible for metabolism of many drugs. CYP1A1 is also present during organogenesis whereas CYP2E1 may be present in some second trimester fetuses. After birth, hepatic CYP2D6, CYP2C8 9, and CYP2C18 19 are activated. CYP1A2 becomes active...
Drug Interactions with Piperine Major Constituent of Black Pepper
Piperine, a major constituent of black and long pepper, has been reported to act as bioavailability enhancer of several drugs by inhibiting drug metabolism and by increasing oral absorption. Bharadwaj et al. reported that piperine inhibits both the drug transported P-glycoprotein and the major drug metabolizing enzyme CYP3A4. Therefore, dietary piperine could affect plasma concentrations of drugs that are substrates of P-glycoprotein or CYP3A4 enzyme especially if administered orally 138 ....
Calcineurin inhibitors
The chemical structures of CsA and tacrolimus, calcineurin inhibitors commonly used in organ transplantation, are shown in Fig. 1. The calcineurin inhibitors block the activation and proliferation of CD4+ and CD8+ T lymphocytes by inhibiting IL-2 production (21,22). Under normal circumstances, binding of major histo compatibility complex-peptide complexes to T-cell receptors results in the formation of an activated form of the calcium calmodulin-dependent serine threonine phosphatase...
Grapefruit Juice and Drug Interactions
It was reported in 1991 that a single glass of grapefruit juice caused a twofold to threefold increase in the plasma concentration of felodipine, a calcium channel blocker, after oral intake of a 5-mg tablet, but a similar amount of orange juice showed no effect (98). Subsequent investigations demonstrated that pharmocokinetics of approximately 40 other drugs are also affected by intake of grapefruit juice (99). The main mechanism for enhanced bioavailability of drugs after intake of grapefruit...
Therapeutic Drug Monitoring of Antidepressants
TCAs, including amitriptyline, doxepin, nortriptyline, imipramine, desipramine, protriptyline, trimipramine, and clomipramine were introduced in the 1950s and the 1960s. These drugs have a narrow therapeutic window, and therapeutic drug monitoring is essential for efficacy of these drugs as well as to avoid drug toxicity. Issues in therapeutic drug monitoring of these drugs are discussed in Chapter 8. The efficacy of lithium in acute mania and for prophylaxis against recurrent episode of mania...

