PMID- 23190184
OWN - NLM
STAT- MEDLINE
DCOM- 20130621
LR  - 20220409
IS  - 1365-2036 (Electronic)
IS  - 0269-2813 (Linking)
VI  - 37
IP  - 3
DP  - 2013 Feb
TI  - Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with 
      Crohn's disease.
PG  - 340-5
LID - 10.1111/apt.12161 [doi]
AB  - BACKGROUND: Methotrexate (MTX) is administered subcutaneously to Crohn's Disease 
      (CD) patients. There are very few studies evaluating the use of oral (PO) MTX in 
      CD. A drug and its pharmaceutical alternative are equivalent (bioequivalence) 
      when the bioavailability of the alternative falls within 80-125% of the 
      bioavailability of the standard (US Food and Drug Administration - FDA). AIM: To 
      compare the pharmacokinetic (PK) profiles of PO and subcutaneous (SC) MTX in CD 
      patients to determine the bioequivalence of these two routes. METHODS: Eleven 
      patients received a PO and an SC MTX dose (25 mg) separated by one week over a 
      two-week interval. Blood samples were collected at specified times over a 24-h 
      period for each patient on two separate days. MTX plasma levels were obtained 
      using sensitive mass spectrometry. Areas under the curve (AUC) were compared 
      between the two routes. RESULTS: The mean AUC values were 3375 ng/mL x h (PO MTX) 
      and 3985 ng/mL x h (SC MTX). The mean AUC ratio (PO/SC) was 0.86 (0.62-1.08). 
      This correlates with a relative PO bioavailability of 86% in comparison to SC. 
      The 90% confidence interval for the mean AUC (PO/SC) ratio is (0.785, 0.929). 
      There were no adverse events. CONCLUSIONS: The mean MTX AUC (PO/SC) in these 
      patients falls outside the 90% confidence interval for the bioequivalence limit. 
      SC MTX is more bioavailable than PO MTX; however, the mean relative MTX 
      bioavailability (PO/SC) nearly met the FDA bioequivalence standard and PO MTX 
      could be proposed in responders who would prefer this route.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Wilson, A
AU  - Wilson A
AD  - Department of Medicine, Division of Gastroenterology, University of Western 
      Ontario, 800 Commissioners Road E., London, ON, Canada. awilson2008@meds.uwo.ca
FAU - Patel, V
AU  - Patel V
FAU - Chande, N
AU  - Chande N
FAU - Ponich, T
AU  - Ponich T
FAU - Urquhart, B
AU  - Urquhart B
FAU - Asher, L
AU  - Asher L
FAU - Choi, Y
AU  - Choi Y
FAU - Tirona, R
AU  - Tirona R
FAU - Kim, R B
AU  - Kim RB
FAU - Gregor, J C
AU  - Gregor JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121128
PL  - England
TA  - Aliment Pharmacol Ther
JT  - Alimentary pharmacology & therapeutics
JID - 8707234
RN  - 0 (Immunosuppressive Agents)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Administration, Cutaneous
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Crohn Disease/drug therapy/*metabolism
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/*pharmacokinetics
MH  - Male
MH  - Methotrexate/administration & dosage/*pharmacokinetics
MH  - Middle Aged
MH  - Ontario
MH  - Therapeutic Equivalency
EDAT- 2012/11/30 06:00
MHDA- 2013/06/25 06:00
CRDT- 2012/11/30 06:00
PHST- 2012/03/21 00:00 [received]
PHST- 2012/04/13 00:00 [revised]
PHST- 2012/10/25 00:00 [revised]
PHST- 2012/11/03 00:00 [accepted]
PHST- 2012/11/30 06:00 [entrez]
PHST- 2012/11/30 06:00 [pubmed]
PHST- 2013/06/25 06:00 [medline]
AID - 10.1111/apt.12161 [doi]
PST - ppublish
SO  - Aliment Pharmacol Ther. 2013 Feb;37(3):340-5. doi: 10.1111/apt.12161. Epub 2012 
      Nov 28.