A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cerezyme Pharmacology, Pharmacokinetics, Studies, Metabolism - Imiglucerase
Cerezyme Pharmacology, Pharmacokinetics, Studies, Metabolism - Imiglucerase
CLINICAL PHARMACOLOGY
Mechanism of Action/Pharmacodynamics
Gaucher disease is characterized by a deficiency of (beta)-glucocerebrosidase
activity, resulting in accumulation of glucocerebroside in tissue macrophages
which become engorged and are typically found in the liver, spleen, and 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 ® (imiglucerase
for injection) 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®.
Pharmacokinetics
During one hour intravenous infusions of four doses (7.5, 15, 30, 60 U/kg)
of Cerezyme ® (imiglucerase for injection) steady-state enzymatic activity
was achieved by 30 minutes. Following infusion, plasma enzymatic activity declined
rapidly with a half-life ranging from 3.6 to 10.4 minutes. Plasma clearance
ranged from 9.8 to 20.3 mL/min/kg, (mean ± S.D., 14.5 ± 4.0 mL/min/kg). The
volume of distribution corrected for weight ranged from 0.09 to 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 one or two patients were studied at each dose level
and infusion rate. The pharmacokinetics of Cerezyme ® do not appear to
be different from placental-derived alglucerase (Ceredase®).
In patients who developed 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).
top
