SC better than oral administration for giving high-dose MTX

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Rheumawire

Apr 8, 2004

SC better than oral administration for giving high-dose methotrexate

Enschede, the Netherlands - Rheumatologists should consider parenteral

administration of high-dose methotrexate (MTX) in rheumatoid arthritis

(RA) patients, according to a new pharmacokinetic analysis in the April

2004 issue of the Journal of Rheumatology that shows that oral MTX

results in limited bioavailability [1].

In fact, bioavailability of higher-dose oral MTX is, on average, only

two thirds that of subcutaneous administration, reports a team of

researchers led by Dr Hoekstra (Medisch Spectrum Twente,

Enschede, the Netherlands).

" Our data suggest that doses between 25 and 40 mg MTX per week,

administered orally, result in limited bioavailability, " they conclude.

" To improve efficacy of MTX at dosages of 25 mg weekly or more, a change

to parenteral administration should be considered. "

Hoekstra et al performed pharmacokinetic analyses on 15 patients with RA

who were taking a stable dose of MTX greater than or equal to 25 mg

weekly. Patients had a median age of 61 and a median disease duration of

7 years.

Pharmacokinetic analysis was performed in each RA patient after oral and

subcutaneous MTX administration and separated by 2 weeks. The median

dose was 30 mg weekly with a range of 25 to 40 mg. All patients also

received folic acid supplementation. Three patients were also using

hydroxychloroquine, 1 chloroquine, 1 sulfasalazine, and 1

aurothiomalate. Eight were using low-dose prednisolone (<10 mg/day), and

11 were using nonsteroidal anti-inflammatory drugs.

Patients were admitted to the hospital in the morning and allowed to

have breakfast at home at least 1.5 hours before they received MTX. Oral

MTX was administered with water, while the subcutaneous MTX was injected

into the upper leg in all patients by the examiner. Blood samples were

drawn before administration and 0.25, 0.5, 0.75, 1.0, 1.25. 1.5, 2, 4,

6, 8, 12, 24, and 48 hours after MTX administration.

MTX serum concentrations were measured by a fluorescence polarization

immunoassay.

MTX bioavailability after oral administration was highly variable and

significantly lower than bioavailability after sc administration. The

mean bioavailability after oral MTX varied between 21% and 96% with a

mean of 64% of that of subcutaneous administration.

The investigators comment that the only other studies of MTX oral doses

>25 mg available for comparison were in patients with malignancies and

that the wide variability in MTX absorption observed in those studies

led to the development of split-dose regimens to improve

bioavailability.

" Bioavailability is enhanced by the subcutaneous route of administration

and this may increase efficacy, " Hoekstra writes, but she warns, " In our

opinion, additional controlled trials are needed to evaluate the effect

of higher doses of MTX, which are in fact widely used in rheumatology

practice. "

Mann

Source

1. Hoekstra M, Haagsma C, Neef C et al. Bioavailability of higher dose

methotrexate comparing oral and subcutaneous administration in patients

with rheumatoid arthritis. J Rheumatol 2004; 31:645-648.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org