Pharmacokinetics and Dose Proportionality of Loratadine

Abstract

The dose proportionality and pharmacokinetics of loratadine, a new nonsedating antihistamine, were studied in 12 normal volunteers. In a three-way cross-over, each volunteer received a single 10-, 20-, or 40-mg loratadine capsule. Blood was collected up to 96 hours after dosing. Plasma loratadine concentrations were determined by radioimmunoassay (RIA), and those of a minor, but active metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Concentrations in the disposition phase were fitted to a biexponential equation for pharmacokinetic analysis. For dose proportionality, AUC- and Cmax-dose relationships were evaluated by linear regression. Also, pharmacokinetic parameters and dose-adjusted AUCs were compared by analysis of variance. Loratadine was rapidly absorbed, reaching Cmax values (4.7, 10.8, and 26.1 ng/mL) at 1.5, 1.0 and 1.2 hours for the 10-, 20-, and 40-mg doses, respectively. The loratadine t1/2 beta ranged from 7.8 to 11.0 hours. Descarboethoxyloratadine reached Cmax values (4.0, 9.9, and 16.0 ng/mL) at 3.7, 1.5, and 2.0 hours for the 10-, 20-, and 40-mg doses, respectively. Its t1/2 beta ranged from 17 to 24 hours. For both compounds, AUC- and Cmax-dose relationships were linear and there were no differences in the t1/2 beta, CL/F, or dose-adjusted AUC values among the treatments. Loratadine and descarboethoxyloratadine plasma concentrations and pharmacokinetics were not dose dependent.

Determination of Lortatadine in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS) and its Pharmacokinetic Application

“…The results of loratadine pharmacokinetic parameters obtained was nearly in accordance with reported literature [19] which stated that T max for loratadine were found to be 1.5hr (range 0.5 to 4.5hr), C max 3.65± 2.82ng/ml, and reported literature [5] which stated that T 1/2 ranges from 3 to 20 hours ( …”

“…Besides, loratadine is available in the market in several dosage forms, namely, tablets, syrup, and rapidly desintigrating tablets [5]. It is contraindicated in patients who are hypersensitive to this medication or to any of its ingredients.…”

Validated ion pair liquid chromatography/fluorescence detection method for assessing the variability of the loratadine metabolism occurring in bioequivalence studies

“…As demonstrated in a previous study, most of the metabolic transformation should be associated with the CYP3A4 activity, but the transformation rate induced by CYP2D6 is five times greater (Yumibe et al, 1996). Reported pharmacokinetic parameters for LOR and DCL obtained after the administration of 20 mg of LOR to Caucasian volunteers have shown a significant variability (Hilbert et al, 1987;Sutherland et al, 2001). This variability is related to genetic polymorphism, as 7-10% of Caucasian individuals posses CYP2D6 expression related to a poor metabolization phenotype (Alvan et al, 1990;Nakamura et al, 1985).…”

“…Different analytical techniques were used, including radioimmunoassay (Hilbert et al, 1987), gas chromatography (Johnson et al, 1994) and HPLC (Sutherland et al, 2001;Zhang et al, 2003;Weng et al, 2003;Chen et al, 2004;Zhong and Blume;Yin et al, 2003). Reported LLOQ values range between 0.01 and 0.2 ng/mL for LOR and 0.025 to 0.2 ng/mL for DCL when liquid chromatography/tandem mass spectrometry is used (Sutherland et al, 2001, Zhang et al, 2003Weng et al, 2003;Chen et al, 2004).…”

Effects of Hydrocortisone on the Pharmacokinetics of Loratadine after Oral and Intravenous Loratadine Administration to Rats

“…Loratadine undergoes extensive first-pass metabolism in the liver to form its major metabolite desloratadine, which also possesses anti-histamine activity and is subject to further metabolism (Hilbert et al, 1987). Desloratadine has greater pharmacological potency than its parent drug (Kreutner et al, 2000;Henz, 2001).…”