The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under- basal conditions a mean ± SE of 1.9 ± 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 ± 0.3 mg (7.2%) primarily due to the increase in gastric volume output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, 1 2β, or the plasma clearance; control values were 3.8 ± 0.5 hr and 1,190 ± 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.
ASJC Scopus subject areas
- Pharmacology (medical)