Pharmacokinetics of a new 5% formulation of hepatitis B immune globulin (H-BIG®)

Risk of HBV infection in a susceptible individual with percutaneous exposure to HBsAg-positive blood or body fluid is between 5-43%. Infants bom to HBsAg-positive mothers are at extreme risk of acquiring HBV, up to 90-92%, with a usual outcome of chronic infection. H-BIG is efficacious in reducing the frequency of HBV infection in both instances. The original formulation of H-BIG (16.5%) is a 15-18% immunoglobulin solution (comprising hyperimmune and normal immune globulin) which contains thimerosal and is not virally-inactivated. A new formulation, H-BIG (5%) 3D contains 5% hyperimmune globulin only, no thimerosal, and is solvent/detergent treated to inactive lipid-enveloped viruses. In a prospective, randomized trial, six subjects received H-BIG 16.5% and seven subjects received H-BIG 5% SD as a single, intramuscular injection of 0.06 mL/kg. Pharmacokinetic parameters have been evaluated by noncompartmental methods through Day 56. The geometric mean C_max was 495.5 RIA units/mL of anti-HBs for H-BIG 16.5% (95% Cl: 374-656) vs 591.6 RIA units/mL (95% Cl: 391-893) for the HBIG 5%SD. Mean t_max was 9.5 days for the 16.5% product and 6.3 days for the 5% product. Geometric mean areas under the anti-HBs time-concentration curves were virtually identical (AUC of 5.70±0.244 and 5.68±0.251, respectively) for the two formulations. These data suggest that the new formulation provides comparable serum anti-HBs levels with equal or superior absorption and persistence in circulation. Formal bioequivalence studies are underway and future studies of the 5% formulation will explore its potential for intravenous administration.