Abbreviations and Acronyms
| Ab | Antibody |
| Abn | Abnormal |
| AFB | Acid-fast bacillus |
| Ag | Antigen |
| AIDS | Acquired immunodeficiency syndrome |
| ALT | Alanine aminotransferase |
| ANA | Antinuclear antibody |
| AST | Aspartate aminotransferase |
| CBC | Complete blood cell count |
| CF | Complement fixation |
| CHF | Congestive heart failure |
| CIE | Counterimmunoelectrophoresis |
| CK | Creatine kinase |
| CNS | Central nervous system |
| CSF | Cerebrospinal fluid |
| CXR | Chest x-ray |
| CYP | Cytochrome P450 |
| Diff | Differential cell count |
| EDTA | Ethylenediaminetetraacetic acid (edetate) |
| ELISA | Enzyme-linked immunosorbent assay |
| GI | Gastrointestinal |
| GNR | Gram-negative rod |
| GNCB | Gram-negative coccobacillus |
| GPC | Gram-positive coccus |
| GVCB | Gram-variable coccobacillus |
| HLA | Human leukocyte antigen |
| Ig | Immunoglobulin |
| IM | Intramuscular(ly) |
| INR | International Normalized Ratio |
| IV | Intravenous(ly) |
| Min | Minute |
| MN | Mononuclear cell |
| MRI | Magnetic resonance imaging |
| N | Normal |
| Neg | Negative |
| NPO | Nothing by mouth (nil per os) |
| PCR | Polymerase chain reaction |
| PMN | Polymorphonuclear neutrophil (leukocyte) |
| PO | Orally (per os) |
| Pos | Positive |
| PTH | Parathyroid hormone |
| RBC | Red blood cell |
| RPR | Rapid plasma reagin (syphilis test) |
| SIADH | Syndrome of inappropriate antidiuretic hormone (secretion) |
| SLE | Systemic lupus erythematosus |
| T3 | Triiodothyronine |
| T4 | Tetraiodothyronine (thyroxine) |
| TSH | Thyroid-stimulating hormone |
| V | Variable |
| VDRL | Venereal Disease Research Laboratory (syphilis test) |
| WBC | White blood cell |
| Wk | Week |
| Yr | Year |
| ↑ | Increased |
| ↓ | Decreased |
| ↔ | No change |
Underlying Assumptions
The basic assumptions underlying therapeutic drug monitoring (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.
| 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: undetectable | 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 | Induces its own metabolism. Metabolite 10,11-epoxide exhibits 13% cross-reactivity by immunoassay. 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 | CHF: 0.5–0.9 ng/mL Atrial fibrillation: 0.5–2 ng/mL | 42; ↑ in uremia, CHF | ↓ in renal dysfunction, CHF, 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 Adult: 50 | 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. Draw trough just before next dose. In uremic patients, some penicillins (eg, carbenicillin, ticarcillin, piperacillin) may decrease gentamicin half-life from 46 hours to 22 hours, posing a risk of reduced antibacterial efficacy. The main adverse reactions are CNS, otic, and renal toxicities. |
| Imipramine | 180–350 ng/mL | 10–16 | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. | |
| Lidocaine | 1–5 mg/L | 1.8; unchanged in uremia, CHF; ↑ in cirrhosis | ↓ in CHF, liver disease | Levels increased with cimetidine therapy. CNS toxicity common in the elderly. |
| Lithium | 0.5–1.5 mmol/L | 22; ↑ in uremia | ↓ in renal dysfunction | Thiazides and loop diuretics may increase serum lithium levels. |
| Methotrexate | 3–10 low dose; 8–15 high dose; ↑ in uremia | ↓ in renal dysfunction | Therapeutic concentrations depend on the treatment protocol (low versus high dose) and time of specimen collection. 7-Hydroxymethotrexate cross-reacts 1.5% in immunoassay. To minimize toxicity, leucovorin or glucarpidase should be continued if methotrexate level is >0.1 mcmol/L at 48 hours after start of therapy. Methotrexate >1 mcmol/L at >48 hours requires an increase in rescue therapy. | |
| Nortriptyline | 50–140 ng/mL | 18–44 | Drug is highly protein-bound. Patient-specific decrease in protein binding may invalidate quoted therapeutic reference interval for effective concentration. | |
| Phenobarbital | 10–40 mg/L | Child: 37–73 Adult: 53–140 ↑in cirrhosis | ↓ in liver disease | Metabolized primarily by the hepatic microsomal enzyme system. Many drug-drug interactions. |
| Phenytoin | 10–20 mg/L; 5–10 mg/L in uremia and severe hypoalbuminemia | Dose/ concentration-dependent | Drug metabolite cross-reacts in immunoassays; the cross-reactivity may be of significance only in the presence of advanced chronic kidney disease. Metabolism is capacity-limited. Increase dose cautiously when level approaches therapeutic reference interval, since new steady-state level may be disproportionately higher. Drug is very highly protein-bound; protein binding is decreased in uremia and hypoalbuminemia. Free drug level (pharmacologically active fraction) may be indicated in certain clinical circumstances. | |
| Sirolimus | Trough: 4–12 ng/mL when used in combination with cyclosporine A; 12–20 ng/mL if used alone | 62 | ↓ in liver dysfunction and with drugs inhibiting CYP3A4 activity | Sirolimus is an immunosuppressant used in combination with cyclosporine and corticosteroids for prophylaxis of organ rejection after kidney transplantation. It has also been used in liver and heart transplantation. When used in combination with cyclosporine, careful monitoring of kidney function is required. Once the initial dose titration is complete, monitoring sirolimus trough concentrations weekly for the first month and every 2 weeks for the second month appears to be appropriate. The optimal time for specimen collection is 24 hours after the previous dose or 0.5 to 1 hour before the next dose (trough level). |
| Tacrolimus | Trough: 8–12 ng/mL | 8.7–11.3 | ↓ in liver dysfunction and with drugs inhibiting CYP3A4 activity | Tacrolimus is used for prophylaxis of organ rejection in adult patients undergoing liver or kidney transplantation and in pediatric patients undergoing liver transplantation. It has also been used to prevent rejection in heart, small bowel, and allogeneic bone marrow transplant patients and to treat autoimmune diseases. Antacid or sucralfate administration should be separated from tacrolimus by at least 2 hours. The optimal time for specimen collection is 12 hours after the previous dose or 0.5 to 1 hour before the next dose (trough level). |
| Theophylline | 5–15 mg/L | 9 | ↓ in CHF, cirrhosis, and with cimetidine | Caffeine cross-reacts 10%. Elimination is increased by 1.5–2 times in smokers. 1,3-Dimethyl uric acid metabolite increased in uremia and, because of cross-reactivity, may cause an apparent slight increase in serum theophylline. |
| Tobramycin | Conventional dosing: Peak: 5–10 mg/L; trough: <2 mg/L High dose once daily: Peak: 20 mg/L; trough: undetectable | 2–3; ↑ in uremia | ↓ in renal dysfunction | Tobramycin, kanamycin, and amikacin may cross-react in immunoassay. Some antibiotics may decrease tobramycin half-life in uremic patients, causing reduced antibacterial efficacy. |
| Valproic acid | 50–100 mg/L | Child: 6–8 Adult: 10–12 | Significant fraction of the drug is protein-bound in vivo (concentration-dependent). Decreased binding in uremia and cirrhosis. | |
| Vancomycin | Trough: 10–20 mg/L | 6; ↑ in uremia | ↓ in renal dysfunction | Ototoxicity in uremic patients may lead to irreversible deafness. Keep peak level <40–50 mg/L to avoid severe toxicity. |
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