Measurement of monoamines and their metabolites in the interstitial fluid of the gut.

Bundles of hollow dialysis fibers were surgically implanted into the submucosa of the stomach and intestine allowing collection of an interstitial fluid (ISF) dialysate. Measurement of monoamines and their metabolites in ISF was performed using high-performance liquid chromatography with electrochemical detection. The local concentration of L-5-hydroxy-tryptophan (5-HTP) in ISF from the antrum was determined in conscious rats after intraperitoneal loading with 5-HTP. The metabolite was similarly evaluated after the administration of levodopa (L-DOPA). Validation of ISF dialysis as a method for determining changes of biogenic amine concentration in the extracellular fluid was determined for the antrum, duodenum, and colon in dogs after the oral or subcutaneous administration of 5-HTP as a precursor of serotonin and 5-hydroxyindole acetyl acetic acid. The proposed procedure provides a novel approach in pharmacologic studies, where a direct correlation between the distribution of a drug and its metabolites (pharmacokinetics) and their effects (pharmacodynamics) has to be measured.