Remicade - Clinical Pharmacology

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In Crohn’s disease, treatment with REMICADE reduced infiltration of inflammatory cells and TNFa production in inflamed areas of the intestine, and reduced the proportion of mononuclear cells from the lamina propria able toexpress TNFa and interferon. After treatment with REMICADE, patients with rheumatoid arthritis or Crohn’s disease exhibited decreased levels of serum IL-6 and C-reactive protein (CRP) compared to baseline. Peripheral blood lymphocytes from REMICADE-treated patients showed no significant decrease in number or in proliferative responses to in vitro mitogenic stimulation when compared to cells from untreated patients.

Pharmacokinetics

Single intravenous (IV) infusions of 3 mg/kg to 20 mg/kg showed a linear relationship between the dose administered and the maximum serum concentration. The volume of distribution at steady state was independent of dose and indicated that infliximab was distributed primarily within the vascular compartment. Median pharmacokinetic results for doses of 3 mg/kg to 10 mg/kg in rheumatoid arthritis and5 mg/kg in Crohn’s disease indicate that the terminal half-life of infliximab is 8.0 to 9.5 days.

Following an initial dose of REMICADE, repeated infusions at 2 and 6 weeks resulted in predictable concentration-time profiles following each treatment. No systemic accumulation of infliximab occurred upon continued repeated treatment with 3 mg/kg or 10 mg/kg at 4- or 8-week intervals. Development of antibodies to infliximab increased infliximab clearance. At 8 weeks after a maintenance dose of 3 to 10 mg/kg of REMICADE, median infliximab serum concentrations ranged from approximately 0.5 to 6 mcg/mL; however, infliximab concentrations were not detectable (<0.1 mcg/mL) in patients who became positive for antibodies to infliximab.

No major differences in clearance or volume of distribution were observed in patient subgroups defined by age, weight, or gender. It is not known if there are differencesin clearance or volume of distribution in patients with marked impairment of hepatic or renal function.A pediatric Crohn’s disease pharmacokinetic study was conducted in 21 patients aged 11 to 17 years old. No notable differences in single-dose pharmacokinetic parameters were observed between pediatric and adult Crohn’s disease patients (see PRECAUTIONS, Pediatric Use).