Enhanced bioavailability and antihistamine effects by transdermal administration of loratadine gels containing an enhancer in rats

The present study examined the feasibility of transdermal administration of loratadine gels containing an enhancer to rats by comparing the pharmacokinetic parameters of loratadine after transdermal, oral, or intravenous administration. Transdermal administration of loratadine gel (12 mg/kg applied to the abdominal skin) with an enhancer produced a significantly higher plasma concentration of loratadine than the loratadine gel without the enhancer (control). The average areas under the serum concentration‐time curves (AUC) was 929±148 h·ng/ml for oral administration, and 3,318±530.9 h·ng/ml for intravenous administration. The AUC of transdermal administration with and without the enhancer was 2,054±328.0 h·ng/ml and 1,094±176.5 h·ng/ml, respectively. The enhancer increased the relative bioavailability by 1.88‐fold (P<0.01). Transdermal application of the loratadine gel containing polyoxyethylene 2‐stearyl ether inhibited the increase in vascular permeability induced by histamine by 28.62%, whereas the loratadine gel without enhancer inhibited the permeability by 20.33%. In conclusion, the loratadine gel system containing an enhancer could be developed as a transdermal delivery system providing the increased constant plasma concentration and antihistamine effects. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.