Comparison of two compartmental models for describing ranitidine's plasmatic profiles

PAULA SCHAIQUEVICH; ADA NISELMAN; MODESTO RUBIO

PHARMACOLOGICAL RESEARCH

Elsevier

Año: 2002 vol. 45 p. 399 - 405

1043-6618

The plasmatic profiles of 12 healthy volunteers after oral administration of ranitidine (150 mg)were studied considering two compartmental models. We observed the presence of two peaks.The proposed mechanism responsible for the existence of secondary peaks includes enterohepaticrecirculation and the existence of multiple sites of absorption along the gastrointestinal tract. Forcharacterizing the pharmacokinetic aspect of the drug, both phenomena were described using twocompartmental models. We calculated the pharmacokinetic parameters and statistical tests afterfitting the data of each volunteer under both models proposed. Statistically significant differenceswere not found in the statistical test values but existed in the area under the curve (AUC) comparingbetween models. To decide which of the two proposed models gave the best approximation of thephysiological phenomenon undergone, we studied the pharmacokinetic of the drug in the rat, ananimal without gallbladder.After oral administration of ranitidine, the plasmatic profile of the animals showed at least twopeaks. Less than 0.2%of an oral dose was recovered in bile as ranitidine. Therefore, and consideringthe rat has no post-absorptive depot from where the drug can be released discontinuously,enterohepatic recycling does not seem to contribute significantly to the occurrence of secondarypeaks in the concentration–time profiles of rats.Considering the results, we proposed that the best model able to explain the plasmaticprofiles found in man and rats after oral administration of ranitidine is the one that presentsmultiple sites of absorption along the gastrointestinal tract. It is important to define the correctmodel in the calculation of the AUC and so in the value of the absolute bioavailability.