The Pharmacokinetics of Loratadine in Normal Geriatric Volunteers

Abstract

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration-time curve, was 146.7 h.ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration-time curve of 394.9 h.ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal, flare and itch in human skin

“…While the reason for the inconsistent efficacy of loratadine is not clear, one possible explanation is a variability in its hepatic metabolism to desloratadine, a compound which possesses 2.5 to 10 times the antihistaminic activity of loratadine in animal models [9,10]. From the work of Hilbert and colleagues [11], peak plasma levels of loratadine occur 1 1 / 2 h after oral dosage while those of desloratadine are stated to occur in under three hours [9]. Thus, while an interval of 4 h between dosing and testing should have been sufficient for the absorption of loratadine and its metabolism to desloratadine, any delay in the hepatic metabolism of the parent drug in some individuals would result in a slower onset of action.…”

Urticária Crónica - Do Diagnóstico ao Tratamento

“…62 De referir, ainda, que poderá haver uma potenciação de efeitos adversos com o uso de ciclosporina e corticoides sistémicos, particularmente em doentes geriátricos com hipertensão arterial e baixa taxa de filtração glomerular. 63 Relativamente às grávidas e lactantes, algumas doentes com UC refratária referem uma resolução espontânea quando engravidam com recorrência no pós-parto, enquanto outras têm agravamento das queixas de urticária durante a gravidez. 64 Embora seja boa prática clínica evitar tratamentos durante a gravidez, nas doentes com sintomas de maior intensidade alguns tratamentos podem ser efetuados sem risco embriogénico ou teratogénico.…”

Application of Kinetic and Dynamic Data for Antihistamines to Risk Characterization in Sensitive Populations

“…The carbamate moiety of loratadine was hydrolyzed to form the active metabolite, descarboethoxyloratadine (desloratadine) (Katchen et al 1985;Hilbert et al 1988). As the parent compound and metabolite are both pharmacologically active, the pharmacokinetic profiles of loratadine and desloratadine were investigated after a single oral dose of 5 mg loratadine was administered to 18 healthy children aged 3.8 + 1.1 years (Salmun et al 2000).…”

“…The same adult volunteers from the previous study also received a 40 mg dose of loratadine after a 1-week washout period of the lower dose. Comparison of pharmacokinetic data for loratadine in the young adults to data in 12 healthy elderly subjects (66 to 78 years; mean + SD not available) who also received a 40 mg dose of loratadine orally (Hilbert et al 1988) indicated that C max values were 3.8-fold higher in the elderly (Table 9). Furthermore, the AUC and t 1/2 , respectively, were 4.1-fold and 4.9-fold higher in subjects with advanced age vs. the young volunteers.…”