Oseltamivir, an Influenza Neuraminidase Inhibitor Drug, Does Not Affect the Steady-State Pharmacokinetic Characteristics of Cyclosporine, Mycophenolate, or Tacrolimus in Adult Renal Transplant Patients

Background: An influenza neuraminidase inhibitor drug, oseltamivir (Os) may be prescribed to renal transplant patients to prevent and treat influenza A and B illness. A pharmacokinetic (PK) interaction between Os and immunosuppressive drugs might adversely affect the efficacy and/or toxicity of the latter agents. This study was conducted to determine whether adverse symptoms and acute drug interactions occur during their coadministration. Materials and Methods: A randomized, crossover study design was utilized to study the effect of a 75-mg dose of Os on the steady-state PK of cyclosporine A (CyA), mycophenolate mofetil, or tacrolimus (Tac) in a convenience sample of 19 adults with a renal allograft by measurement of total plasma or blood drug concentrations (C-p) over one 12-hour dose interval. Os PK parameters were determined from its concentrations and those of its metabolite, Os carboxylate, in plasma and urine over 48 hours. Results: Of 19 volunteers, 12 were men, with age (mean +/- SD) 46 +/- 11 years, weight 83 +/- 19 kg, and calculated Cl-creatinine 64 +/- 27 mL/min. Adverse effects were minor and transient. Os did not affect the steady-state C-max, T-max, or area under the concentration versus time curve (AUC) over a 12-hour dose interval of CyA, mycophenolic acid, or Tac or the C-trough of CyA or mycophenolate but increased the mean C-trough of Tac by 13%. Discussion: The increase in Tac mean C-trough during coadministration with Os is not likely clinically important. Os and Os carboxylate PK were similar to those in subjects with native kidneys and similar renal function who have been described in the literature. Conclusions: These data from a single Os dose study suggest that coadministration is not expected to cause adverse symptoms nor alter the steady-state PK of CyA, mycophenolate mofetil, or Tac in stable adult renal transplant patients with mild renal insufficiency. The data enable a multiple-dose study that reflects clinical practice during influenza exposure and assesses the possibility that chronic exposure to Os might result in a different outcome.