LORAPAED ALLERGY RELIEF Oral solution Ref.[50137] Active ingredients: Loratadine

Absorption

Loratadine is rapidly and well-absorbed. Concomitant ingestion of food can delay slightly the absorption of loratadine but without influencing the clinical effect. The bioavailability parameters of loratadine and of the active metabolite are dose proportional.

Distribution

Loratadine is highly bound (97% to 99%) and its active metabolite moderately bound (73% to 76%) to plasma proteins.

In healthy subjects, plasma distribution half-lives of loratadine and its active metabolite are approximately 1 and 2 hours, respectively.

Biotransformation

After oral administration, loratadine is rapidly and well absorbed and undergoes an extensive first pass metabolism, mainly by CYP3A4 and CYP2D6. The major metabolite-desloratadine (DL)- is pharmacologically active and responsible for a large part of the clinical effect. Loratadine and DL achieve maximum plasma concentrations (T_max) between 1-1.5 hours and 1.5-3.7 hours after administration, respectively.

Elimination

Approximately 40% of the dose is excreted in the urine and 42% in the faeces over a 10 day period and mainly in the form of conjugated metabolites. Approximately 27% of the dose is eliminated in the urine during the first 24 hours. Less than 1% of the active substance is excreted unchanged in active form, as loratadine or DL.

The mean elimination half lives in healthy adult subjects were 8.4 hours (range=3 to 20 hours) for loratadine and 28 hours (range-8.8 to 92 hours for the major active metabolite).

Renal impairment

In patients with chronic renal impairment, both the AUC and peak plasma levels (C_max) increased for loratadine and its metabolite as compared to the AUCs and peak plasma levels (C_max) of patients with normal renal function. The mean elimination half-lives of loratadine and its metabolite were not significantly different from that observed in normal subjects. Haemodialysis does not have an effect on the pharmacokinetics of loratadine or its active metabolite in subjects with chronic renal impairment.

Hepatic impairment

In patients with chronic alcoholic liver disease, the AUC and peak plasma levels (C_max) of loratadine were double while the pharmacokinetic profile of the active metabolite was not significantly changed from that in patients with normal liver function. The elimination half-lives for loratadine and its metabolite were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease.

Elderly

The pharmacokinetic profile of loratadine and its active metabolite is comparable in healthy adult volunteers and in healthy geriatric volunteers.

Loratadine and its active metabolite are excreted in the breast milk of lactating women.

Preclinical data reveal no special hazard based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive toxicity studies, no teratogenic effects were observed. However, prolonged parturition and reduced viability of offspring were observed in rats at plasma levels (AUC) 10 times higher than those achieved with clinical doses.