Quantitative measurement ofbiliary excretion andof gall bladder concentration ofdrugs under physiological conditions inman

SUMMARY Gallbladder storage ofhepatic bile prevents complete recoveryofbiliary excretion of drugs tobeobtained underphysiological conditions inman. Theaimofthis study wastodevelop and validate amethod forsimultaneous measurement ofgall bladder storage ofacholephilic drug, andof itsduodenal excretion andt½/, inbile. Duodenal perfusion using polyethylene glycol asintestinal recoverymarker formeasurement ofdrugduodenal excretion, with an ivbolus of""TcHIDAfor measurement ofdrug masswithin thegall bladder wasused. Gallbladder volume wasmeasured by ultrasonography. T./2 inbile was measured byrelating drugduodenal excretion tothatofbile acid usedasan endogenous bile marker. Theuseofbile acid asbiliary marker was validated intwo subjects receiving simultaneous ivinfusion ofindocyanine green.Sevenhealthy subjects were studied using abeta-lattam antibiotic, Cefotetan 1giv, astest drug. Medianvalues during thestudy period (seven hours) were51F1 mg forCefotetan duodenal excretion, 452mg forgall bladder mass and2-8mg/mlforconcentration within thegall bladder. T½, ofthedruginbile was100minutes. This technique enables measurement ofmass andconcentration ofdrugswithin thegall bladder tobe carried out,inaddition tomeasurements oft½/, ofdrugsinbile. Thesemeasurements may have specific application forassessment ofpotential efficacy ofantibiotics inbiliary tract infections, as well asgeneral application forassessment ofbiliary excretory kinetics ofdrugs.