A 6-month mixed-effect pharmacokinetic model for post-transplant intravenous anti-hepatitis B immunoglobulin prophylaxis

BACKGROUND: Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG) therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation. METHODS: Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose. RESULTS: HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L). CONCLUSION: The variability (explained and unexplained) in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon patient characteristics should be adjusted focusing quantitatively on the early post-transplant period.