Cerezyme Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Gaucher disease is characterized by a deficiency of β-glucocerebrosidase activity, resulting in accumulation of glucocerebroside in tissue macrophages which become engorged and are typically found in the liver, spleen, bone marrow and occasionally, in lung, kidney and intestine. Secondary hematologic sequelae include severe anemia and thrombocytopenia in addition to the characteristic progressive hepatosplenomegaly, skeletal complications, including osteonecrosis and osteopenia with secondary pathological fractures. Cerezyme catalyzes the hydrolysis of glucocerebroside to glucose and ceramide. In clinical trials, Cerezyme improved anemia and thrombocytopenia, reduced spleen and liver size and decreased cachexia to a degree similar to that observed with Ceredase.
Pharmakokinetics: During 1-hr IV infusions of 4 doses (7.5, 15, 30, 60 U/kg) of Cerezyme, steady-state enzymatic activity was achieved by 30 min. Following infusion, plasma enzymatic activity declined rapidly with a half-life ranging from 3.6-10.4 min. Plasma clearance ranged from 9.8-20.3 mL/min/kg (mean±SD, 14.5±4 mL/min/kg). The volume of distribution corrected for weight ranged from 0.09-0.15 L/kg (0.12±0.02 L/kg). These variables do not appear to be influenced by dose or duration of infusion. However, only 1 or 2 patients were studied at each dose level and infusion rate. The pharmacokinetics of Cerezyme do not appear to be different from placental-derived aglucerase (Ceredase).
In patients who developed immunoglobulin G (IgG) antibody to Cerezyme, an apparent effect on serum enzyme levels resulted in diminished volume of distribution and clearance and increased elimination half-life compared to patients without antibody (see Warnings).