Abstract:

The extended-release pesudoephedrine/loratadine twice-daily combination tablet formulation has been shown to be safe and effective for the relief of symptoms associated with allergic rhinitis. Each tablet consists of laratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, of which 60 mg i s in a barrier-protected core. We have established an LC-ESI-MS method for si multaneous determination of pesudoephedrine/loratadine and its metabolite(DCL) i n human plasma, which was proved to be sensitive,accurate and convenient. By th is means, we have investigated the characteristic of its pharmacokinetics in hum an. In the two study periods, subjects received a single dose and multiple doses (days 1 to 6) of twice-daily formulation. After a single dose, the main pharm acokinetics parameters of t_1/2, t_max, c_max, and AUC_0-36 were (6.9±1.4)h,(4.3±3.2)h,(311.3±50.2)μg·L^-1 a nd(4 312±678)μg·(h·L)^-1 for pseudoephedrine;(6.8±1.7)h,(1.4 ±0.4)h,(2.46±1.88)μg·L^-1 and(8.93±6.19)μg·(h·L)^-1 for lor a tadine;(15.6±4.7)h,(2.0±1.0)h,(2.76±1.80)μg·L^-1 and(20.63±1 1.33)μg·(h·L)^-1 for DCL, respectively. After multiple doses (days 1 to 6), the main pharmacokinetics parameters of Cav, DF, and AUCss were (337.4±49.4)μg·L^-1, (0.72±0.28)% and(4 049±594)μg·(h·L)^-1 for ps eudoep hedrine; (0.86±0.74)μg·L^-1, (3.05±1.37)% and (10.38±8.86)μg·(h·L)^-1 for loratadine; (1.31±0.76)μg·L^-1, (2.18±0.82)% and (15.69±9.14)μg·(h·L)^-1 for DCL, respectively.In conclusion, Loratadine is extensively metabolized in the liver to an active m etabolite(DCL), so first pass has resulted in obvious difference within the vo lunteers. In contrast with the common formulation, this twice-daily combination tablet formulation has showed the character of extended-release. After a singe l dose, t_1/2 and t_max of pesudoephedrine have been increased, and the same time, c_max has been reduced. After multiple doses, DF of pesudoephedrine was little. The time-concentration curve of pesudoephedrine sulfate has two peaks, which wa s the proof of immediate-extended release coating.