Does Gastric Bypass Result in Reduced Absorption of Methotrexate?

For example, Chenhsu et al described the need to double the dose of cyclosporine to achieve therapeutic levels in a patient with decompensated cirrhosis as a complication of jejunoileal bypass who subsequently underwent liver transplant.⁸ In patients who have had gastric bypass surgery, the route of administration of methotrexate (MTX) may need special consideration.

In a retrospective analysis of eight of our rheumatology patients who underwent gastric bypass via the Roux en Y procedure, we found that patients who could tolerate MTX did better switching to injectable MTX. Nonetheless, all eight patients were started on a biologic agent. The question arises: Would the patients have needed to be advanced to biologic therapy if they had been tried on parenteral MTX first (see Tables 1 and 2)?

Subcutaneous MTX

In one recent study, Schiff et al suggested subcutaneous (SC) MTX may be most effective in patients receiving oral MTX who are experiencing an inadequate clinical response.⁹ In this phase 2 study examining the effectiveness of SC MTX vs. oral MTX, the researchers reported that the dose of the oral MTX reached a plateau at 15 mg, whereas there was no plateau with the SC MTX. Thus, SC MTX provided higher systemic exposure to MTX than comparable oral doses. Relative bioavailability, as measured by area under the curve (AUC) of SC MTX vs. oral MTX at doses of 10, 15, 20 and 25 mg, was 121%, 114%, 131% and 141%, respectively. The ratio of the dose-normalized AUC (0–24 h) and Cmax of SC MTX vs. oral MTX were 127.61 (90% CI: 122.30–133.15) and 94.88 (90% CI: 87.95–102.37). These observations appear to be consistent with the clinical experience of many practitioners who have noted a benefit to using parenteral rather than oral MTX.

Rheumatology is fast becoming a specialty of complex immunology and targeted genetic therapies. To best serve our patients, rheumatology health professionals should carefully scrutinize all treatment modalities and drug bioavailabilities, especially among those patients who have undergone gastric bypass surgery.

Iris Zink, NP, has worked in the Rheumatology Department at the Beals Institute in Lansing, Mich., for 15 years. She is the president elect of the Rheumatology Nurses Society and co-authored the chapter in the Rheumatology Nurses Society core curriculum on HIV and arthritis. She is also adjunct faculty at Michigan State University.

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