The purpose of this study is to compare the safety and pharmacokinetic properties (the absorption, distribution and excretion) of two preparations of aminopterin (0.25 mg tablets and 1.0 mg tablets) following oral administration by subjects with moderate to severe psoriasis.

Inclusion Criteria:

• Give written informed consent by signing an IRB-approved Informed Consent.

• Be under treatment for at least moderate to severe psoriasis (diagnosis confirmed by a dermatologist) with MTX (10-20 mg per week) for a minimum of 3 months. Moderate to severe psoriasis is defined here as plaque-type psoriasis affecting a body surface area > 10%.

• Be 21 years of age or older, but not 60 years of age or older.

• If participant is female of child bearing potential, then subject must indicate that she is not pregnant.

• Must be fully informed of the potential for AMT to adversely affect a fetus, and must agree to use highly effective method of birth control beginning at the time of consent, during the study, and for 3 months after leaving the study.

• Women of childbearing potential may enter the study only after a confirmed menstrual period, and must have a negative urine pregnancy test at the time of screening and within 24 hours of each study drug dose.

• Have adequate hematologic function as evidenced by the following :results obtained from a blood sample drawn within 2 days of day 0:

  • WBC > 4,500/ mm3
  • Platelet Count > 150,000/mm3
  • Hemoglobin > 12.0 gm/dL

• Have adequate liver function as evidenced by the following results obtained from a blood sample drawn within 2 days of day 0:

  • AST (SGOT) ≤ 40 IU/L
  • ALT (SGPT) ≤ 40 IU/L
  • Alkaline Phosphatase ≤ 120 IU/L
  • Total Bilirubin ≤ 1.2 mg/dL

• Have adequate renal function as evidenced by the following result obtained from a blood sample drawn within 2 days of day 0:

  • GFR estimated by Cockcroft-Gault formula:
  • > 90 ml/min (male)
  • > 90 ml/min (female)

• Have no detectable urine glucose, urine ketones, or urine protein from a sample obtained within 2 days of day 0.

• Weight of 35 to 90 kg.

Exclusion Criteria:

• A known history of hepatitis, liver fibrosis or cirrhosis (grades IIIA, IIIB or IV), diabetes (type I or II), HIV infection, tuberculosis, interstitial lung disease, or an abnormal screening chest x-ray that is consistent with interstitial lung disease.
• Known peptic ulcer, ulcerative colitis or Crohn's disease.
• Body mass index (BMI) <19.0 or > 35.0 (see appendix C).
• Within 2 weeks prior to randomization use of any of the following medications that may result in drug/drug interactions with aminopterin: methotrexate, trimethoprim with or without sulfamethoxazole; sulfonamides; sulfonylureas; pyrimethamine; triamethamine; dipyridamole; colchicine; probenecid; aminoglycosides; theophylline; phenytoin; and folinic acid (i.e., leucovorin) unless prescribed by the investigator to treat study drug related toxicity.
• Within 2 weeks prior to randomization use of salicylates, non-steroidal anti-inflammatory (NSAID) drugs, including Over-The-Counter nonprescription use of aspirin, ibuprofen or naproxen.
• Use of medications that may be negatively influenced by regular folic acid supplementation such as the anti-epileptics phenobarbital, diphenylhydantoin, and primidone.
• Use of any investigational medication within 30 days prior to admission to the study.
• Inability to abstain from alcohol during the study.
• A history of substance abuse, drug addiction or alcoholism.
• Unwillingness to use an adequate form of contraception during the study and for 3 months after the study.
• A female who is pregnant, intends to become pregnant during the study (or within 6 months after study completion), or nursing.
• Concurrent participation in another clinical trial involving experimental treatment.
• Current and uncontrolled infection, cardiovascular, pulmonary, hepatic or GI conditions that will interfere with the conduct of the trial or pose an additional morbid risk.
• Any renal conditions that will interfere with the conduct of the trial or pose an additional morbid risk.
• Any concurrent disease or condition that in the opinion of the investigator impairs the subject's ability to complete the trial. Psychological, familial, sociological, geographical or medical conditions which, in the Investigator's opinion, could compromise compliance with the objectives and procedures of this protocol or obscure interpretation of the trial's data.