The relative bioavailability of loratadine administered as a chewing gum formulation in healthy volunteers.
OBJECTIVE
The aim of this study was to investigate the pharmacokinetics of loratadine and its active metabolite desloratadine after single-dose administration of loratadine as a conventional tablet, orally disintegrating tablet (smelt tablet) and a chewing gum formulation with and without the collection of saliva.


METHODS
Twelve healthy male volunteers participated in a four-period cross-over trial evaluating the effect of dosage forms on the pharmacokinetics of a single dose of loratadine. Loratadine was administered as two 10-mg conventional tablet, two 10-mg smelt tablet, a 30-mg portion of medicated chewing gum without collection of saliva and a 30-mg portion of medicated chewing gum with collection of saliva. Blood samples were taken at predefined sampling points 0-24 h after medication, and the plasma concentrations of loratadine and desloratadine were determined by high-performance liquid chromatography. Each study period was separated by a wash-out period of at least 7 days.


RESULTS
The mean dose-corrected area under the plasma concentration-time curve extrapolated to infinity AUC(0-infinity) for the chewing gum formulation was statistically significantly increased compared to the tablet formulation (geometric mean ratio: 2.68; 95%CI: 1.75-4.09). Desloratadine pharmacokinetic parameters from the chewing gum formulation were not statistically significantly different from the conventional tablet. Neither loratadine nor desloratadine pharmacokinetics of the smelt tablet formulation were statistically significantly different from the conventional tablet formulation. Plasma concentrations of desloratadine following the administration of loratadine as chewing gum with saliva collection were very low.


CONCLUSIONS
Our study showed that formulation of loratadine as a medicated chewing gum results in an almost threefold increase in relative bioavailability. This is most likely due to a bypass of first-pass metabolism as this study suggests that approximately 40% of the absorbed loratadine was absorbed via the oral mucosa.
Noehr-Jensen
Lene
L
Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Winslowparken 19, Denmark. lnjensen@health.sdu.dk
Damkier
Per
P
Bidstrup
Tanja Busk
TB
Pedersen
Rasmus Steen
RS
Nielsen
Flemming
F
Brosen
Kim
K
D000327:Adsorption; D000328:Adult; D001682:Biological Availability; D002638:Chewing Gum; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D017336:Loratadine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D013607:Tablets
D002638:Chewing Gum; D039563:Histamine H1 Antagonists, Non-Sedating; D013607:Tablets; D017336:Loratadine; C121345:desloratadine