Dose-related bioavailability of bromelain and trypsin after repeated oral administration

Donath F., Mai I., Maurer A., Brockmöller J., Kuhn C.-S., Friedrich G., Roots I.

Institute of Clin. Pharmacol., Charité
Humboldt-Univ., Berlin
Pharmbiodyn, Denzlingen, Germany

American Society for Clinical Pharmacology and Therapeutics 1997, 61(2), PI-79, pp 157.

572 KA 

At present there exists relatively little knowledge on the absorption of macromolecules from the intestine into the systemic circulation. Nevertheless, proteolytic enzymes with a molecular weight higher than 20 kD are usually orally given for the prevention and treatment of posttraumatic edema. A therapeutic effect has been shown; but in which chemical and functional conformation these enzymes pass the gut wall is not known yet. In this study the influence of two different doses on the bioavailability of bromelain and trypsin was investigated.
In a double blind, randomised and crossover designed manner, the enzyme preparation was orally administered in doses of 400 mg or 800 mg respectively, four times daily over four days to 21 healthy male volunteers. Blood samples were collected immediately before each dosing and for two days after the last dose. In the plasma, functionally intact bromelain and trypsin was measured by using ELISA, western blot and the corresponding specific hydrolytic activity. Trough levels and AUC data of trypsin, bromelain and their corresponding specific hydrolytic activity increased in a dose related order. A close correlation between the trypsin plasma concentration and the respective specific hydrolytic activity in the blood could be observed, proving the absorption of intact proteins.