Apixaban

Plasma

1 mL

0.5 mL (Note: This volume does not allow for repeat testing.)

Blue-top (sodium citrate) tube (preferred), lavender-top (EDTA) tube, or green-top (heparin) tube

Measurement of drug level in order to monitor therapeutic level and/or diagnose under-dosage or potential toxicity.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

See table.¹

Apixaban is an oral anticoagulant that prevents thrombin generation by inhibiting factor Xa produced as the result of both the intrinsic and extrinsic coagulation pathways.^4-6 Apixaban inhibits both free and clot-bound factor Xa and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non- valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism.^4,7 This drug inhibits free and prothrombinase-associated factor Xa in a concentration-dependent manner.^8,9 Apixaban has a rapid onset, reaching a maximal plasma concentration within one to three hours after oral administration.^10,11 Steady-state concentrations are reached within three days with a half-life of 9 to 14 hours in healthy adults.^10-11 Oral bioavailability of apixaban is not affected by food intake.^9,10 Apixaban is almost insoluble in water and exhibits high plasma protein binding (87%) in humans.¹¹ Approximately one-fourth of apixaban is excreted by the kidneys and about one-half by fecal route.^10,11 Significant renal impairment results in decreased clearance and increases overall exposure to the drug.¹¹

The P-glycoprotein (P-gp) multidrug transporter protein facilitates the transport of apixaban across cell membranes and influences the absorption and disposition of the drug in vivo. Apixaban is metabolized by the mixed function oxidase, cytochrome P450 3A4/5 (CYP3A4/5).¹⁰ Drugs that affect the activity of CYP3A4/5 and P-gp can potentially affect the pharmacokinetic profile of apixaban.

Routine therapeutic monitoring of apixaban level is not required because of the drug's relatively wide therapeutic index.⁴ Despite the use of fixed doses of apixaban, determination of the amount drug present in a given individual may be valuable in several clinical situations.^12-23 Measurement of levels can inform clinicians with concerns regarding patient compliance and adherence to therapy. Apixaban is transported across the intestinal wall by P-glucoprotein, and drugs that induce or inhibit P-glycoprotein activity may decrease or increase the levels of apixaban, respectively. Therapeutic monitoring can help the clinician assess the potential cause of bleeding or thrombosis while on therapy. Determination of levels may also be useful in preparation for surgery or an invasive procedure. Also, drug levels measurement can be valuable in determining drug accumulation in situations of renal or hepatic failure and when administered with other drugs that may alter metabolism or clearance.

Apixaban is measured using a validated liquid chromatography-mass spectrometry (LC/MS-MS) method. LC/MS-MS serves as the criterion standard for exact quantification of concentrations of direct oral anticoagulant (DOAC) medications and is considered to be the most accurate method for measurement of these drugs.^{16,19,20,24,25} Use of liquid LC/MS-MS provides highly accurate measurement of apixaban concentrations without the variable interferences associated with traditional clot-based and chromogenic assays.²⁶ In fact, studies performed using the Labcorp LC/MS-MS method indicates the assayed drug recovery was unaffected by the presence of lupus anticoagulants or heparin administration. Factor VIII deficiency and multiple factor deficiency associated with Coumadin treatment had no effect on the recovery of drug. Plasma peak concentration of apixaban following a single 5-mg dose had a median value of 96 ng/mL with a +/- two standard deviation range of 40-152 ng/mL (n=20).^26,27