RESEARCH - Splitting high-dose oral MTX improves bioavailability

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J Rheumatol. 2006 Jan 15; [Epub ahead of print]

Splitting High-Dose Oral Methotrexate Improves Bioavailability: A

Pharmacokinetic Study in Patients with Rheumatoid Arthritis.

Hoekstra M, Haagsma C, Neef C, Proost J, Knuif A, van de Laar M.

OBJECTIVE: To study the bioavailability of a divided higher oral dose of

methotrexate (MTX), in comparison to a single dose, in adult patients with

rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed

in 10 patients with RA taking a stable dose (25-35 mg weekly) of MTX.

Separated by one week, a pharmacokinetic analysis was performed in each

patient after an oral single dose, and after an equal but split dose

separated by 8 hours. MTX serum concentrations were measured by a

fluorescence polarization immunoassay technique. Analysis was performed by

calculation of the area under the curve (AUC) by the trapezoidal rule and by

means of an iterative 2-stage Bayesian population procedure, obtaining

population and individual pharmacokinetic parameters. For the population

analysis, data from 15 patients in our previous study comparing oral and

subcutaneous administration of MTX were also used. RESULTS: The median MTX

dose was 30 mg weekly (range 25-35 mg). The bioavailability of the split

dose was 28% higher compared to the single dose (p = 0.007). In the

population pharmacokinetic modeling, a 2-compartment model best described

the serum MTX concentration versus time curves. The mean bioavailability

after single-dose and split-dose MTX was 0.76 and 0.90, respectively,

compared to subcutaneous administration. There was a statistically

significant difference in the bioavailability of the 2 oral administration

regimens (p = 0.008).

CONCLUSION: The bioavailability of oral higher dose MTX in adult patients

with RA can be improved by splitting the dose.

PMID: 16463431

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6463431 & dopt=Abstract

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