Kinetic investigations intothepossible cause oflow serum histidine inrheumatoid arthritis

SUMMARY Toinvestigate thecause oflowserum histidine inrheumatoid arthritis (RA)single oral andintravenous doses ofL-histidine were administered topatients withactive RA,andtoan equal numberofage andsex matched control subjects. Inthefirst study13patients andtheir controls received a 100mg kg-1doseofL-histidine as an aqueous slurry. Significant differences were seen inbodyweight, predose baseline serum histidine concentration, Cmax,t,½,andarea under curve,AUCOoInasecond study sixpatients andsixcontrols eachreceived a 50mg kg-1 doseofL-histidine bothorally andintravenously on two separateoccasions. Thepatients with RA hada lowerbaseline serum histidine concentration, a lowervolumeofdistribution, anda shorter plasma half life thanthecontrols, butthese differences were notstatistically significant. Nodifference was seeninbioavailability or clearance. Lowserum histidine inRA isunlikely to beduetomalabsorption fromthegut,uptake byabnormal gutflora, or increased metabolism.