Rituximab (Rituxan): Pharmacodynamics and Pharmacokinetics

Introduction to Rituxan (Rituximab)

Rituximab, marketed under the brand name Rituxan, is prescribed for the treatment of non-Hodgkin's lymphoma (NHL), rheumatoid arthritis (RA), and chronic lymphocytic leukemia. The drug comes with stern warnings of dangerous reactions, including serious infections, heart problems, kidney problems, stomach and bowel problems — some of which "can lead to death" (Rituxan.com). Under the prescribing directions issued by the manufacturer, the clinical pharmacology section is organized around three components: mechanism of action, pharmacodynamics, and pharmacokinetics.

Pharmacodynamics in NHL and RA Patients

In patients suffering from non-Hodgkin's lymphoma, studies revealed that administering Rituxan produced a depletion of tissue-based B cells. The first study, involving 166 patients, showed that circulating CD19-positive B cells were depleted within the first three weeks of treatment. This depletion continued for six to nine months after treatment. Regarding B-cell recovery, 83% of those 166 patients began recovering B cells approximately six months after treatment, and median B-cell levels returned to normal roughly one year after receiving Rituxan.

Fourteen percent of patients treated with Rituxan had IgM and/or IgG serum levels below the normal range from five to eleven months after treatment.

For patients with rheumatoid arthritis, treatment with Rituxan led to the depletion of peripheral B lymphocytes. The majority of RA patients experienced near-complete depletion — defined as CD19 counts below the lower limit of quantification (20 cells/µL) — within two weeks of their first dose. Most patients maintained peripheral B-cell depletions for at least six months after the first dose, though approximately 4% experienced depletion lasting more than three years. RA patients also showed reductions in inflammation markers such as interleukin-6 (IL-6) and C-reactive protein (CRP), among others.

Two hundred and three NHL patients received 375 mg/m² of Rituxan intravenously each week for four weeks. Rituxan was detectable in patients' serum up to six months following those intravenous administrations. The pharmacokinetic profile of Rituximab when given as six infusions of 375 mg/m², combined with six cycles of CHOP chemotherapy, was consistent with the profile observed when Rituximab was used alone.

Pharmacokinetics and Dosing Profile

When 298 NHL patients received six infusions of Rituxan — either once weekly or once every three weeks — the estimated median terminal elimination half-life was 22 days, with a range of 6.1 to 52 days. Patients with higher CD19-positive cell counts experienced higher drug clearance rates.

For patients with rheumatoid arthritis, B cells are understood to play a role in the pathogenesis of the disease, potentially acting at multiple sites in the autoimmune and inflammatory process. When RA patients received two doses of Rituxan, mean drug concentrations following the first and second infusions were 157 (±46; 29%). Among 2,005 RA patients who received Rituxan, the estimated clearance of Rituximab was 0.335 L/day, the volume of distribution was 3.1 L, and the mean terminal elimination half-life was 18.0 days, with individual values ranging from 5.17 to 77.5 days — a notably wide distribution.

It is worth noting that weight, age, and gender had no effect on the pharmacokinetics of Rituxan in patients with rheumatoid arthritis.

Should Rituxan be taken with food? Genentech, the pharmaceutical company that manufactures Rituxan, reports that there are no special rules for what patients can eat or drink before, during, or after an infusion. The general advice is to eat before the infusion or bring a snack, and to check with treating physicians ahead of time to confirm what foods may be appropriate.