Tinzaparin Pharmacokinetics in Patients with Cancer: A Comparative Modeling Study

Cancer-associated thrombosis (CAT) is common and a leading cause of mortality in patients with cancer. In specific CAT scenarios, low-molecular-weight heparins (LMWHs), including tinzaparin, are preferred over direct oral anticoagulants. Despite the importance of understanding LMWH pharmacokinetics (PK) in cancer for optimizing CAT management, available data remain limited.To compare tinzaparin PK in cancer and non-cancer patients by developing a population PK model.This prospective, multicenter, case-: control trial enrolled patients receiving once-daily subcutaneous tinzaparin at a therapeutic dose of 175 IU·kg^-1, including matched cancer and non-cancer patients. Plasma anti-Xa activity was measured at multiple time points and analyzed using a non-linear mixed-effect modeling. A PK model was developed, and covariate effects were assessed for parameters of the model. The impact of cancer on tinzaparin PK was evaluated by incorporating cancer status as a categorical covariate.A total of 333 patients (including 46 matched cancer and non-cancer patients) were included in the analysis. A monocompartmental model with first-order absorption best described tinzaparin PK. The volume of distribution was associated with body weight, while clearance and anti-Xa activity were associated with creatinine clearance. No significant differences were observed between matched cancer and non-cancer patients in anti-Xa activity exposure at day 1 and steady state.PK profiles were comparable between cancer and non-cancer patients. Additionally, further studies should clarify the role of renal function in guiding tinzaparin dosing.