title: Influence of food on the oral bioavailability of loratadine and pseudoephedrine from extended-release tablets in healthy volunteers.
abstract: The effect of a high-fat breakfast on the bioavailability of the components of an extended-release tablet containing 10 mg loratadine in the immediate-release coating and 240 mg pseudoephedrine sulfate in the extended-release core was studied in 24 healthy male volunteers in a single-dose, two-way crossover study. The drug was administered after a 10-hour overnight fast or within 5 minutes of consuming a standardized high-fat breakfast. Serial blood samples were collected over a 48-hour period, and plasma was analyzed for loratadine and its active metabolite descarboethoxyloratadine (DCL), and pseudoephedrine. For pseudoephedrine, maximum concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUCzero-infinity) were similar after both treatments, indicating no relevant food effect on the bioavailability of pseudoephedrine. Also, the absorption profiles of pseudoephedrine (from Wagner-Nelson analysis) were similar for the fed and fasted treatments, indicating no apparent differences in absorption. Plasma concentration-time profiles and values for Cmax and AUCzero-infinity of DCL were similar for the two treatments, indicating no relevant food effect on the pharmacokinetics of DCL. In contrast, for loratadine, administration with food resulted in a significantly increased mean Cmax (53%) and AUC from time zero to the final quantifiable sample (AUCif) (76%). However, the resultant Cmax and AUC of loratadine under fed conditions were well below those previously obtained at steady-state after multiple-dose administration of loratadine (40 mg/day) that were shown to be safe and well-tolerated in several clinical studies. The effect of food on the bioavailability and pharmacokinetic profiles of the components of a combination loratadine/pseudoephedrine extended-release tablet is not likely to be clinically significant.
authors.affiliation: Department of Drug Metabolism, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Nomeir
authors.forename: P
authors.initials: P
authors.lastname: Mojaverian
authors.forename: T
authors.initials: T
authors.lastname: Kosoglou
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
authors.forename: J
authors.initials: J
authors.lastname: Nezamis
authors.forename: E
authors.initials: E
authors.lastname: Rodwanski
authors.forename: C C
authors.initials: CC
authors.lastname: Lin
authors.forename: M N
authors.initials: MN
authors.lastname: Cayen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D002845:Chromatography; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004809:Ephedrine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D017336:Loratadine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D014662:Vasoconstrictor Agents; D017336:Loratadine; D004809:Ephedrine