The Pharmacokinetic Responses of Humans to 20 g of Alanyl-Glutamine Dipeptide Differ with the Dosing Protocol but Not with Gastric Acidity or in Patients with Acute Dengue Fever

Abstract

Pharmacokinetic responses to oral doses of the dipeptide, L-alanyl-glutamine (Ala-Gln), were evaluated after a single, bolus load or an intermittent dosing in normal healthy subjects (n = 8) to find the optimal mode of oral administration. In a subgroup (n = 4) of the healthy subjects, the influence of a gastric acid suppressor (Omeprazole) was investigated. The influence of an acute episode of classic Dengue fever was examined in eight patients. All modes of administration to healthy subjects significantly increased free plasma Gln and alanine concentrations. Peak increments of plasma Gln concentration were 794+/-107 micromol/L (mean +/- SEM) after bolus intake of 20 g of Ala-Gln and 398+/-61 micromol/L after intermittent intake of the same cumulative dosage of the dipeptide (P<0.01). After intermittent dosing, the maximum peak increase appeared significantly later (P<0.01). Areas under the curve (AUC), expressing the integrated responses over time of plasma free Gln and alanine concentrations, did not differ after bolus and intermittent loads of Ala-Gln. Pretreatment with the acid suppressor, Omeprazole, did not influence Gln (P = 0.79) or alanine (P = 0.90) plasma increment. Dengue patients manifested the same pharmacokinetic responses to a 20 g Ala-Gln bolus as healthy controls. In general, on a micromolar concentration basis, Gln and alanine followed parallel tracks in terms of plasma appearance, clearance and elimination after the oral administration of 20 g of the Ala-Gln dipeptide through the range of conditions and dosing protocols explored here.