Intestinal absorption kinetics of amiodarone in rat small intestine

Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic effects. These seem to be related, at least in part, to the pharmacokinetics of the drug and particularly to some features of its gastrointestinal absorption process. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes, but its low aqueous solubility can act as the rate limiting step for absorption, making the process erratic and variable. In order to gain an insight into the intestinal absorption mechanism of the drug and detect possible non-linearities, a series of experiments using a classical rat gut in situ preparation were carried out with three amiodarone hydrochloride solutions (10, 75, and 200 micrograms mL-1). A synthetic non-ionic surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a rapid, sensitive technique that was validated. The amiodarone first-order absorption rate constants obtained in these conditions were similar. No significant differences between ka values were found. Amiodarone absorption was clearly identified as a passive diffusion process.