title: Pharmacokinetics of loratadine and pseudoephedrine following single and multiple doses of once- versus twice-daily combination tablet formulations in healthy adult males.
abstract: The pharmacokinetic profiles of single and multiple doses of loratadine, descarboethoxyloratadine (DCL) (the major active metabolite of loratadine), and pseudoephedrine were determined in a randomized, open-label, two-way crossover study in 24 healthy men. Subjects received a single dose (day 1) and multiple doses (days 3 to 10) of a once-daily (QD) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLAR-ITIN-D 24 HOUR tablets), and a twice-daily (BID) formulation of loratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, with 60 mg in an immediate-release coating and 60 mg in the barrier-protected core (CLARITIN-D 12 HOUR tablets) in study sessions, each separated by a 10-day washout period. Both regimens were safe and well tolerated. On day 1, plasma loratadine, DCL, and pseudoephedrine concentrations were higher following the QD formulation than following the BID formulation, as expected. On day 10, loratadine and DCL maximum plasma concentration (Cmax) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulation; however, the values of the area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) for loratadine and DCL were equivalent (90% confidence interval [CI]: 83% to 110% for loratadine; 90% to 107% for DCL). On day 10, pseudoephedrine Cmax and AUC0-24 values were equivalent (90% CI for Cmax: 94% to 109%; for AUC: 91% to 106%) for the two formulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrine formulations produced equivalent loratadine and DCL AUC0-24 values and equivalent pseudoephedrine Cmax and AUC0-24 values following multiple dosing. The lower pseudoephedrine concentrations in the evening with the QD formulation may minimize the potential for insomnia in patients when compared with the BID formulation.
authors.affiliation: Clinical Pharmacology Department, Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kosoglou
authors.forename: E
authors.initials: E
authors.lastname: Radwanski
authors.forename: V K
authors.initials: VK
authors.lastname: Batra
authors.forename: J M
authors.initials: JM
authors.lastname: Lim
authors.forename: D
authors.initials: D
authors.lastname: Christopher
authors.forename: M B
authors.initials: MB
authors.lastname: Affrime
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004809:Ephedrine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006634:Histamine H1 Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D017336:Loratadine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D013607:Tablets; D017336:Loratadine; D004809:Ephedrine