CYP3A Activity and Rivaroxaban Serum Concentrations in Russian Patients with Deep Vein Thrombosis

Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters.

The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months. During the study period, Doppler ultrasound was performed weekly to assess the clot dynamics and recanalization time.

We found a direct statistically reliable correlation between CYP3A4 activity and both peak and trough rivaroxaban levels. A correlation was also found between the initial clot length and the time to full recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found between either the glomerular filtration rate and peak rivaroxaban concentrations or between CYP3A4 activity and the treatment effectiveness parameters. No connection between renal function and rivaroxaban concentration was established in our study, which agrees with the clinical trials data that allow unlimited rivaroxaban use in patients with glomerular filtration rate >30 mL/min.

The direct link between the initial clot length and time to full recanalization that has been found means that patients with more advanced stages of thrombosis need more time to reach recanalization than their counterparts with a less severe condition.