The basic assumptions underlying therapeutic drug monitoring (see Table 4–1) are that drug metabolism varies from patient to patient and that the plasma level of a drug is more closely related to the drug’s therapeutic effect or toxicity than is the dosage. For certain drugs that are intended for long-term use (see Table 4–2), close monitoring with appropriate routine hematology and chemistry tests may be necessary to avoid or minimize drug-associated adverse events.
TABLE 4–1.THERAPEUTIC DRUG MONITORING.1 |Favorite Table|Download (.pdf) TABLE 4–1. THERAPEUTIC DRUG MONITORING.1
|Drug ||Effective Concentrations ||Half-Life (hours) ||Dosage Adjustments ||Comments |
|Amikacin || |
Peak: 20–30 mg/L; trough: <10 mg/L
High dose once daily:
Peak: 60 mg/L; trough: <5 mg/L
|2–3; ↑ in uremia ||↓ in renal dysfunction ||Concomitant kanamycin or tobramycin therapy may give falsely elevated amikacin results by immunoassay. |
|Amitriptyline ||95–250 ng/mL ||9–25 || ||Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. |
|Carbamazepine ||4–12 mg/L ||10–15 ||↓ in severe renal or hepatic disease || |
Induces its own metabolism.
Metabolite 10,11-epoxide exhibits 13% cross-reactivity by immunoassay and is pharmacologically active. Adverse reactions: skin reactions, myelosuppression.
|Cyclosporine ||100–300 mcg/L (ng/mL) whole blood ||6–12 ||↓ in renal dysfunction, liver disease ||Cyclosporine is lipid-soluble (20% bound to leukocytes; 40% to erythrocytes; 40% in plasma, highly bound to lipoproteins); the binding is temperature-dependent in vitro and concentration-dependent in vivo. HPLC and LC-tandem mass spectrometry methods are highly specific for parent drug and considered the gold standard assays. Monoclonal fluorescence polarization immunoassay (FPIA) and monoclonal chemiluminescence immunoassay also measure cyclosporine reliably; polyclonal immunoassays are less specific owing to cross-reaction with drug metabolites. Anticonvulsants and rifampin increase metabolism. Erythromycin, ketoconazole, and calcium channel blockers decrease metabolism. The main adverse reaction is concentration-related nephrotoxicity. |
|Desipramine ||100–250 ng/mL ||13–23 || ||Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. |
|Digoxin || |
HF: 0.5–0.9 ng/mL
Atrial fibrillation: 0.5–2 ng/mL
|36–42; ↑ in uremia, HF ||↓ in renal dysfunction, HF, hypothyroidism; ↑ in hyperthyroidism || |
Bioavailability of digoxin tablets is 50–90%.
Specimen must not be drawn within 4 hours of an intravenous dose or 6 hours of an oral dose.
Dialysis does not remove a significant amount.
Hypokalemia potentiates toxicity.
Digitalis toxicity is a clinical and not a laboratory diagnosis.
Digibind (digoxin-specific antibody) therapy of digoxin overdose can interfere with measurement of digoxin levels depending on the digoxin assay.
Elimination reduced by amiodarone, quinidine, and verapamil.
|Ethosuximide ||40–100 mg/L || |
| ||Levels used primarily to assess clinical response and compliance. Toxicity is rare and does not correlate well with plasma concentrations. |
|Gentamicin || |
Conventional dosing: Peak: 4–8 mg/L; trough: <2 mg/L
High dose once daily: Peak: 20 mg/L; trough: undetectable
|2–3; ↑ in uremia (7.3 during dialysis) ||↓ in renal dysfunction || |
Draw peak specimen (conventional dosing) 30 minutes after end of 30- to 60-min infusion.