title: Single-dose administration of Bowman-Birk inhibitor concentrate in patients with oral leukoplakia.
abstract: The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor and a potential cancer chemopreventive agent for humans. In this Phase I clinical trial, BBI concentrate was administered as a single oral dose to 24 subjects with oral leukoplakia. Pharmacokinetics of BBI was analyzed, and subjects were monitored clinically for toxic effects. Subjects received between 25 and 800 chymotrypsin inhibitor units (CIU) of the compound in a dose escalation trial. BBI was taken up rapidly, and a metabolic product of BBI was excreted in the urine within 24-48 h. No clinical or laboratory evidence of toxicity was observed in the study. Protease activity was also measured in buccal cells to evaluate usefulness as a biomarker. Single-dose BBI concentrate administered up to 800 CIU was well tolerated and appeared to be nontoxic. Further investigation in Phase II clinical trials is being done.
authors.affiliation: Department of Otolaryngology, Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange 92868, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Armstrong
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: X S
authors.initials: XS
authors.lastname: Wan
authors.forename: J
authors.initials: J
authors.lastname: Atiba
authors.forename: C E
authors.initials: CE
authors.lastname: McLaren
authors.forename: F L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000284:Administration, Oral; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000652:urine; D015415:Biomarkers / Q000032:analysis; D018890:Chemoprevention; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D010450:Endopeptidases / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007972:Leukoplakia, Oral / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000652:urine; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000652:urine
chemical_list: D016588:Anticarcinogenic Agents; D015415:Biomarkers; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D010450:Endopeptidases; D002918:Chymotrypsin