Pharmacokinetics of subcutaneous methotrexate.

Abstract

The pharmacokinetics of subcutaneously administered methotrexate was studied as a parenteral alternative to oral administration. An initial feasibility study was performed in Rhesus monkeys comparing the subcutaneous route to intravenous (IV) injection and oral administration. The subcutaneous dose was completely absorbed and a sustained-release effect was observed when compared with the IV dose. No local or systemic toxicities resulted from subcutaneous methotrexate in the animals. Twelve children with acute lymphoblastic leukemia on maintenance therapy protocols prescribing either 7.5 mg/m2 biweekly or 40 mg/m2 weekly were also monitored after both a subcutaneous and an oral dose of methotrexate. Four children at the higher dosage level were also studied after an equal IV dose. The subcutaneous dose was again completely absorbed in these children at both dose levels, whereas the oral dose, which produced comparable plasma drug concentrations at the lower dosage level, resulted in a total drug exposure (area under the plasma concentration-time curve) that was one third that of the equal subcutaneous dose at the higher dosage level. No local or systemic toxicity was attributed to the subcutaneous methotrexate. Subcutaneous administration of methotrexate is well tolerated and well absorbed and appears to overcome the problems associated with oral administration, including variable absorption and saturation of the absorption mechanism with increasing doses.

The pharmacokinetics of methotrexate and its 7‐hydroxy metabolite in patients with rheumatoid arthritis.

“…Although the kinetics of MTX following high doses for the treatment of neoplastic disease have been studied extensively, studies of intermittent low-dose MTX treatment have been restricted to the first 24 h after dosing and plasma drug concentrations throughout the dosage interval have not been reported (Balis et al, 1983;Christophidis et al, 1979;Edelman et al, 1984;Evans et al, 1982;Furst et al, 1986;Herman et al, 1989;Pearson et al, 1987;Shen & Azarnoff, 1978;Sinett et al, 1989;Teresi et al, 1989;Wang & Fujimoto, 1984). In most of the reported studies MTX was measured by immunological assay and consequently plasma concentrations of 7-OHMTX could not be determined.…”

The absorption of low‐dose methotrexate in patients with inflammatory bowel disease

“…12±14 Oral absorption is apparently dose-dependent, since low doses of MTX (less than 12± 30 mg/m 2 ) were reported to be better absorbed than higher doses. 15,16 It has been shown that about twothirds of an oral dose of MTX reaches the systemic circulation. 13 Pinkerton et al 17 have shown that oral absorption of MTX can be substantially reduced by food; however, there are at least two studies which have demonstrated that bioavailability of the drug is largely independent of food intake.…”

Preference, satisfaction and usability of subcutaneously administered methotrexate for rheumatoid arthritis or psoriatic arthritis: results of a postmarketing surveillance study with a high-concentration formulation

“…Clinical data support the use of subcutaneously (SC) administered MTX that is well absorbed, well tolerated, and appears to solve some of the issues encountered with oral administration, e.g. variable absorption and saturation of the absorption mechanism with increasing doses [Balis et al 1988]. A 24-week SC administration of MTX at a dose of 15 mg/week was significantly more effective than oral administration [Braun et al 2008].…”