Panos Macheras1,2,3, Pavlos Chryssafidis4,5. 1. PharmaInformatics Unit, ATHENA Research Center, Athens, Greece. macheras@pharm.uoa.gr. 2. Department of Pharmaceutical Sciences, State University of New York (SUNY), Buffalo, New York, USA. macheras@pharm.uoa.gr. 3. Department of Pharmacy, National and Kapodistrian University of Athens, University Campus, 15771, Athens, Greece. macheras@pharm.uoa.gr. 4. PharmaInformatics Unit, ATHENA Research Center, Athens, Greece. 5. Department of Pharmacy, National and Kapodistrian University of Athens, University Campus, 15771, Athens, Greece.
Abstract
ABSRACT: PURPOSE: To demonstrate that oral drug absorption is terminated in finite time. To develop models based on biopharmaceutical/physiological and finite absorption time concepts. METHODS: The models are based on i) the passive drug diffusion mechanism under the sink conditions principle ii) the rate limiting role of the drug's properties solubility and permeability and iii) the relevant restrictions associated with the gastrointestinal transit times of drug in the stomach, the small intestines and the colon. Two input functions of constant rate are considered for the absorption of drug from i) the stomach/small intestines with an upper limit of 5 h and ii) the colon with an upper limit of 30 h. Branched differential equations were written for the time course of drug in the body. RESULTS: Simulations were performed using different scenarios, assuming a variety of drug properties and limited or non-existent absorption from the colon. Literature oral data of cephradine, ibuprofen, flurbiprofen and itraconazole were analyzed. For all drugs examined, nice fittings of the branched differential equations to the experimental data were observed. CONCLUSIONS: For all drugs the absorption process was terminated in the small intestine. The meaning of partial AUCs, Cmax, tmax are questioned. Applications of these models to IVIVC are anticipated.
ABSRACT: PURPOSE: To demonstrate that oral drug absorption is terminated in finite time. To develop models based on biopharmaceutical/physiological and finite absorption time concepts. METHODS: The models are based on i) the passive drug diffusion mechanism under the sink conditions principle ii) the rate limiting role of the drug's properties solubility and permeability and iii) the relevant restrictions associated with the gastrointestinal transit times of drug in the stomach, the small intestines and the colon. Two input functions of constant rate are considered for the absorption of drug from i) the stomach/small intestines with an upper limit of 5 h and ii) the colon with an upper limit of 30 h. Branched differential equations were written for the time course of drug in the body. RESULTS: Simulations were performed using different scenarios, assuming a variety of drug properties and limited or non-existent absorption from the colon. Literature oral data of cephradine, ibuprofen, flurbiprofen and itraconazole were analyzed. For all drugs examined, nice fittings of the branched differential equations to the experimental data were observed. CONCLUSIONS: For all drugs the absorption process was terminated in the small intestine. The meaning of partial AUCs, Cmax, tmax are questioned. Applications of these models to IVIVC are anticipated.
Entities:
Keywords:
finite absorption time; oral drug absorption; pharmacokinetics, BCS, BDDCS