RESEARCH - Pharmacokinetics of oral MTX in patients with RA

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Arthritis Rheum. 2008 Oct 30;58(11):3299-3308.

Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis.

Dalrymple JM, Stamp LK, O'Donnell JL, Chapman PT, Zhang M, Barclay ML.

University of Otago, Christchurch, New Zealand.

OBJECTIVE: There is evidence supporting a therapeutic range for

methotrexate polyglutamate (MTXGlu) concentrations in the treatment of

rheumatoid arthritis (RA). Knowledge of the pharmacokinetics of

MTXGlu(1-5) is required for optimal timing of blood sampling. The aim

of this study was to determine the time to steady state and the

half-life of accumulation of red blood cell (RBC) MTXGlu(1-5) in

patients with RA commencing oral MTX, and the time for RBC MTXGlu(1-5)

to become undetectable and the half-life of elimination of RBC

MTXGlu(1-5) in patients ceasing treatment with oral MTX.

METHODS: Ten patients beginning treatment and 10 patients stopping

treatment with low-dose oral MTX were recruited. Blood samples were

initially collected weekly, with gradual extension to monthly

collection over the study period. RBC MTXGlu(1-5) concentrations were

assayed by high-performance liquid chromatography. Results were

analyzed using a first-order exponential method.

RESULTS: The median times to reach steady state in RBCs (defined as

90% of the maximum concentration) were 6.2, 10.6, 41.2, 149, and 139.8

weeks, respectively, for MTXGlu(1), MTXGlu(2), MTXGlu(3), MTXGlu(4),

and MTXGlu(5). The median half-life of accumulation for RBC

MTXGlu(1-5) ranged from 1.9 weeks to 45.2 weeks. The median times for

MTXGlus to become undetectable in RBCs were 4.5, 5.5, 10, 6, and 4

weeks, respectively, for MTXGlu(1), MTXGlu(2), MTXGlu(3), MTXGlu(4),

and MTXGlu(5). The median half-life of elimination for RBC MTXGlu(1-5)

ranged from 1.2 weeks to 4.3 weeks.

CONCLUSION: There is wide interpatient variability of RBC MTXGlu(1-5)

accumulation and elimination in adults with RA. These data also

suggest that after a dose change, >6 months are required for RBC

MTXGlu(1-5) to reach steady state. Such delays in achieving steady

state suggest that more rapid dose escalation or subcutaneous

administration from the outset should be considered.

PMID: 18975321

http://www.ncbi.nlm.nih.gov/pubmed/18975321

Not an MD

[Guest guest]

Evidently the answer is no, which is good to know.

Stan,

Seattle, cloudy and foggy.

--------- Re: [ ] RESEARCH - Pharmacokinetics of oral MTX in patients

with RA

Which reminds me, occassionally before being diagnosed I gave blood when demand

became critical, being O-Neg, which is fairly common no one was that excited.

But now I am wondering if those of us with RA should give blood, and/or would

they even accept it? Just curious.

Stan

Seattle, Foggy, very foggy.

------------ -- Original message ------------ --

From: " " <Rheumatoid.Arthriti s.Support@ gmail.com>

Pharmacokinetics of Oral Methrotrexate in Patients With Rheumatoid Arthritis

Medscape

Posted 01/16/2009

Methotrexate (MTX) is commonly used to treat rheumatoid arthritis (RA)

and is suggested as the " anchor " drug in treating the disease. Despite

its widespread use, the understanding of its mechanism of action and

pharmacokinetics is limited. Since joint damage occurs early in the

course of RA and is largely irreversible, understanding the time it

takes for stable levels of MTX to be reached could be useful in

effectively controlling RA and preventing long-term damage. A new

study examining levels of MTX metabolites in red blood cells was

published in the November issue of Arthritis & Rheumatism

(http://www3. interscience. wiley.com/ journal/76509746 /home).

MTX is normally taken orally and is rapidly taken up into a variety of

cells, including red blood cells, where it remains long after being

eliminated from blood serum. Once inside red blood cells, the drug can

assume up to five different forms, which are known as MTXGlu1-5 (MTX

polyglutamates) These can be measured inside red blood cells and are

thought to be representative of concentrations within other cells,

such as lymphocytes. Within the cell, MTX polyglutamates bind to and

inhibit several important enzymes, playing a role in a number of

anti-inflammatory actions and pathways. The dose of MTX varies and is

unpredictable from patient to patient, but because it disappears

rapidly from blood plasma, measurement in plasma can't be used to

monitor concentrations of the drug. However, MTX polyglutamate

concentrations can be measured in red blood cells. Patients with RA

are normally started on low doses of MTX, with increasing amounts

based on response to treatment, but valuable time may be lost with

this method, resulting in unnecessary joint damage.

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Read the entire article here:

http://www.medscape .com/viewarticle /585493

Not an MD