title: Small intestinal bacterial overgrowth and warfarin dose requirement variability.
abstract: The dose of warfarin needed to obtain a therapeutic anticoagulation level varies widely among patients and can undergo abrupt changes for unknown reasons. Drug interactions and genetic factors may partially explain these differences. Intestinal flora produces vitamin K2 (VK2) and patients with small intestinal bacterial overgrowth (SIBO) rarely present reduced INR values due to insufficient dietary vitamin K. The present study was undertaken to investigate whether SIBO occurrence may affect warfarin dose requirements in anticoagulated patients. Based on their mean weekly dose of warfarin while on stable anticoagulation, 3 groups of 10 patients each were defined: low dose (LD, <or=17.5 mg/wk of warfarin); high dose (HD, from 35-70 mg/wk); and very high dose (VHD>or=70 mg/wk). Each patient underwent a lactulose breath test to diagnose SIBO. Plasma levels of warfarin and vitamin K-analogues were also assessed. Patients with an altered breath test were 50% in the VHD group, 10% in the HD group, and none in the LD group (P=0.01). Predisposing factors to SIBO were more frequent in the VHD group, while warfarin interfering variables were not. VHD patients were younger and had a higher plasma vitamin K1 (VK1) concentration (P>0.05). On the contrary, the plasma VK2 levels tended to be lower. This pilot study suggests that SIBO may increase a patient's warfarin dose requirement by increasing dietary VK1 absorption through the potentially damaged intestinal mucosa rather than increasing intestinal VK2 biosynthesis. Larger studies are needed to confirm these preliminary data and to evaluate the effects of SIBO decontamination on warfarin dosage.
authors.affiliation: Gastrointestinal and Hepatology Section, Department of Clinical and Experimental Medicine, Ospedale S. Maria della Misericordia, and Department of Biochemistry Science and Molecular Biotechnologies, University of Perugia, Italy. vittorio.giuliano@unipg.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Giuliano
authors.forename: Gabrio
authors.initials: G
authors.lastname: Bassotti
authors.forename: Evangelia
authors.initials: E
authors.lastname: Mourvaki
authors.forename: Danilo
authors.initials: D
authors.lastname: Castellani
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Filippucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sabatino
authors.forename: Stefania
authors.initials: S
authors.lastname: Gizzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Palmerini
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
authors.forename: Olivia
authors.initials: O
authors.lastname: Morelli
authors.forename: Monia
authors.initials: M
authors.lastname: Baldoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Morelli
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D001944:Breath Tests; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000382:microbiology*; D007792:Lactulose; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014812:Vitamin K / Q000008:administration & dosage; D010837:Vitamin K 1 / Q000494:pharmacology; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D007792:Lactulose; D014859:Warfarin; D010837:Vitamin K 1