Methods: For testing of clinical samples, plasma was obtained from normal healthy volunteers (NHV; n= 20) at defined time intervals following a 3h infusion of a single 1200 mg dose of ORI in a Phase 1 study. For in vitro testing, ORI was spiked into human plasma over a concentration range of 2 to 47 µg/ml. PL-dependent CT included prothrombin time (PT), activated partial thromboplastin time (APTT), Dilute Russell Viper Venom Test (DRVVT), activated clotting time (ACT), silica clot time (SCT) and activated Protein C Resistance (APCR). PL-independent CT included chromogenic anti-factor Xa (anti-FXa), thrombin time (TT) and an assay to diagnose heparin-induced thrombocytopenia (anti-heparin-PF4). The TtR of each test interference was the interval from the start of the ORI infusion to the time the result returned to the normal reference range.
Results: Transient prolongation of PT, APTT, DRVVT, ACT and SCT occurred in plasma samples obtained from NHVs in the phase 1 study (table). Using ORI-spiked human plasma in vitro, prolongation of coagulation in the affected tests occurred in a concentration-dependent manner. ORI did not interfere with assays for APCR, anti-FXa, TT, or anti-heparin-PF4.
Conclusion: Although ORI has no effect of the coagulation system, it can cause artificial elevations in some laboratory CT. Because of its single-dose regimen, the transient interference of ORI on these CT does not require further consideration beyond the specified TtR of test interference in contrast to some LG and LP antibiotics that require daily administration.
|Coagulation test||Time-to-resolution (hours) of test interference in normal healthy volunteers that received a single 1200 mg infusion of oritavancin|
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