PHARMACOKINETICS OF LORATADINE AND PSEUDOEPHEDRINE FOLLOWING SINGLE AND MULTIPLE DOSES OF ONCE-DAILY VERSUS TWICE-DAILY COMBINATION TABLET FORMULATIONS IN HEALTHY ADULT MALES

The pharmacokinetic profiles of single and multiple doses of loratadin e, descarbo-ethoxyloratadine (DCL) (the major active metabolite of lor atadine), and pseudoephedrine were determined in a randomized, open-la bel, two-way crossover study in 24 healthy men. Subjects received a si ngle dose (day 1) and multiple doses (days 3 to 10) of a once-daily (Q D) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLARITIN- D(R) 24 HOUR tablets), and a twice-daily (BID) formulation of loratadi ne 5 mg in an immediate-release coating and pseudoephedrine sulfate 12 0 mg, with 60 mg in an immediate-release coating and 60 mg in the barr ier-protected core (CLARITIN-D(R) 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 followin g the BID formulation, as expected. On day 10, loratadine and DCL maxi mum plasma concentration (C-max) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulat ion; however, the values of the area under the plasma concentration-ti me curve from 0 to 24 hours (AUC(0-24)) for loratadine and DCL were eq uivalent (90% confidence interval [CT]: 83% to 110% for loratadine; 90 % to 107% for DCL). On day 10, pseudoephedrine C-max and AUC(0-24) equ ivalent (90% CI for C-max 109%; for AUC: 91% to 106%) for the two form ulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrin e formulations produced equivalent loratadine and DCL AUC(0-24) values and equivalent pseudoephedrine C-max and AUC(0-24) values following m ultiple dosing. The lower pseudoephedrine concentrations in the evenin g with the QD formulation may minimize the potential for insomnia in p atients when compared with the BID formulation.