The effect of CYP1A induction on amiodarone disposition in the rat

A Physiologically Based Pharmacokinetic Model of Amiodarone and its Metabolite Desethylamiodarone in Rats: Pooled Analysis of Published Data

“…Among them, the study by Elsherbiny and co-workers contained tissue distribution data following multiple IV doses (25 mg/kg daily for consecutive 4 days) of AMD administered to male Sprague-Dawley rats [39]. The other five studies [31,38,[40][41][42] contained plasma or blood pharmacokinetics of AMD and/or DEA under various dosing regimens, such as post IV bolus of AMD, IV bolus of DEA, or IV infusion of AMD, at different dose levels.…”

“…5b). All the concentration data points collected from the model evaluation references [31,[38][39][40][41][42] were compared to those simulated by the model. As shown in Fig.…”

“…Pharmacokinetic data from six studies [31,[38][39][40][41][42] (Table 1) were used to evaluate the rat PBPK model. Simulations were conducted after setting BW and dosage as the same as those in the literature, and then were compared to the observed time course of AMD and DEA in tissues.…”

“…Six studies [31,[38][39][40][41][42] were used to evaluate the PBPK model (Table 1). Among them, the study by Elsherbiny and co-workers contained tissue distribution data following multiple IV doses (25 mg/kg daily for consecutive 4 days) of AMD administered to male Sprague-Dawley rats [39].…”

A liquid chromatography-mass spectrometry method for nicotine and cotinine; utility in screening tobacco exposure in patients taking amiodarone

“…This may have consequences on the toxicity profile of amiodarone (AM), which remains the most effective antiarrhythmic drug for a number of cardiac arrhythmias. AM is metabolized to a number of metabolites by CYP, including its major circulating metabolite, desethylamiodarone (DEA) (Elsherbiny and Brocks, ). This metabolite is considered to have a toxicity profile which is more severe than that of the parent drug (Bargout et al , ).…”