Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules.
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PMID:Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule. 234 2

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in the management of liver transplant recipients. MMF inhibits the inosine monophosphate dehydrogenase that has been shown to have in vitro antiviral properties against flaviviruses, suggesting the possibility that it might also inhibit the hepatitis C virus (HCV). The goal of this short-term dose escalation study was to assess the antiviral effects of MMF on HCV replication. Patients with chronic hepatitis C who had not undergone liver transplantation were randomized to 8 weeks of treatment with one of four mycophenolate dose regimens (1000 mg orally twice daily, 500 mg orally twice daily, 250 mg orally twice daily, or a matched oral placebo twice daily). All groups were double-blinded. Quantitative HCV RNA levels and serum alanine aminotransferase were assessed at baseline, at weeks 2, 4, and 8 of dosing, and at weeks 4 and 8 of follow-up. Thirty patients met inclusion criteria, enrolled, and were randomized. HCV RNA levels did not change significantly during treatment. Specifically, no subject became virus negative or had a one-log decrease in virus level. Serum aminotransferase level did not normalize in any subject. The most common side effects were headache, nausea, and diarrhea. Mycophenolate alone does not appear to have a significant antiviral or biochemical effect in patients with chronic hepatitis C.
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PMID:Lack of antiviral effect of a short course of mycophenolate mofetil in patients with chronic hepatitis C virus infection. 1251 74