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Home Books Guide to Diagnostic Tests, 7e

Chapter 4: Drugs

Diana Nicoll; Chuanyi Mark Lu

UNDERLYING ASSUMPTIONS

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
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TABLE 4–1. THERAPEUTIC DRUG MONITORING.1
Drug Effective Concentrations Half-Life (hours) Dosage Adjustments Comments
Amikacin

Conventional dosing:

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

Child: 30–40

Adult: 50–60

 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.

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