Transporters and drug–drug interactions: Important determinants of drug disposition and effects

Low molecular weight heparins (LMWH) are recommended for thromboprophylaxis in ICU patients but often fail to reach adequate peak anti-Xa activity.To compare the pharmacokinetic profiles of intravenous (IV) versus subcutaneous (SC) route of administration of LMWH.This was a prospective, monocentric, randomized trial. Patients were randomized to the IV route of administration with a 4-h infusion of nadroparin 3800 IU or to the SC route of administration. Randomization was stratified according to the need for vasopressor or not. Anti-Xa activity was measured at baseline, and at 1, 2, 4, 6, 8, 12 and 24 h after the administration was started.Sixty patients were included, of whom 30 were randomized to the IV group and 30 to the SC route. Pharmacokinetic profiles were significantly different. Mean peak anti-Xa activity was 0.38 IU/ml in the IV group vs 0.20 IU/ml in the SC group (p < 0.001). Trough values and AUC (0-24 h) were similar in both groups. Pharmacokinetic profiles were similar whether patients received vasopressors or not.The IV route of administration with a 4-h infusion lead to a significantly higher peak anti-Xa activity without affecting trough value or the AUC (0-24 h). Whether the IV administration of LMWH might improve the efficacy of thromboprophylaxis requires further research.Registration: ClinicalTrials.gov, NCT04982055, retrospectively registered 08 July 2021, https://clinicaltrials.gov/ct2/show/NCT04982055?cond=NCT04982055&draw=2&rank=1