Rituxan at a dose of 375 mg/m²was administered as an IV infusion at weekly intervals for 8 doses to 37 patients with NHL.¹⁵ The mean Cmax after 8 infusions was 550 µ g/mL (range, 171-1177 µ g/mL). The mean Cmax increased with each successive infusion through the eighth infusion (Table 1).

Table 1: Rituximab Cmax Values

The pharmacokinetic profile of Rituxan when administered as 6 infusions of 375 mg/m²in combination with 6 cycles of CHOP chemotherapy was similar to that seen with Rituxan alone.¹⁶

Following the administration of 2 doses of Rituximab in patients with rheumatoid arthritis, the mean Cmax values were 183 mcg/mL (CV = 24%) for the 2 x 500 mg dose and 370 mcg/mL (CV = 25%) for the 2 x 1000 mg dose, respectively. Following 2 x 1000 mg Rituximab dose, mean volume of distribution at steady state was 4.3 L (CV = 28%). Mean systemic serum clearance of Rituximab was 0.01 L/h (CV = 38%), and mean terminal elimination half-life after the second dose was 19 days (CV = 32%).

Special Populations

Gender

The female patients with RA (n = 86) had a 37% lower clearance of Rituximab than male patients with RA (n = 25). The gender difference in Rituximab clearance does not necessitate any dose adjustment because safety and efficacy of Rituximab do not appear to be influenced by gender.

The pharmacokinetics of Rituximab have not been studied in children and adolescents. No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of Rituximab.

Pharmacodynamics

Administration of Rituxan resulted in a rapid and sustained depletion of circulating and tissue-based B-cells. Lymph node biopsies performed 14 days after therapy showed a decrease in the percentage of B-cells in seven of eight patients with NHL who had received single doses of Rituximab ≥ 100 mg/m².¹⁰ Among the 166 patients in the pivotal NHL study, circulating B-cells (measured as CD19-positive cells) were depleted within the first three doses with sustained depletion for up to 6 to 9 months post-treatment in 83% of patients.¹⁴ Of the responding patients assessed (n = 80), 1% failed to show significant depletion of CD19-positive cells after the third infusion of Rituximab as compared to 19% of the nonresponding patients. B-cell recovery began at approximately 6 months following completion of treatment. Median B-cell levels returned to normal by 12 months following completion of treatment.¹⁴

There were sustained and statistically significant reductions in both IgM and IgG serum levels observed from 5 through 11 months following Rituximab administration. However, only 14% of patients had reductions in IgM and/or IgG serum levels, resulting in values below the normal range.¹⁴

In RA patients, treatment with Rituxan induced depletion of peripheral B lymphocytes, with all patients demonstrating near complete depletion within 2 weeks after receiving the first dose of Rituxan. The majority of patients showed peripheral B-cell depletion for at least 6 months, followed by subsequent gradual recovery after that timepoint. A small proportion of patients (4%) had prolonged peripheral B-cell depletion lasting more than 3 years after a single course of treatment.

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