The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children aged 2 to 5 years.
OBJECTIVE
We assessed the pharmacokinetics and tolerability of 5 mg loratadine syrup (1 mg/mL) in children aged 2 to 5 years.


METHODS
Two studies were undertaken. A single-dose, open-label bioavailability study was performed to characterize the pharmacokinetic profiles of loratadine and its metabolite desloratadine. Plasma concentrations of loratadine and desloratadine were determined at 0, 1, 2, 4, 8, 12, 24, 48, and 72 hours after a single administration of 5 mg loratadine syrup to 18 healthy children (11 male, 7 female; 12 black, 5 white, 1 other; mean age +/- SD, 3.8 +/- 1.1 years; mean weight +/- SD, 17.4 +/- 4.4 kg). In addition, a randomized, double-blind, placebo-controlled, parallel-group study was performed to assess the tolerability of 5 mg loratadine syrup after multiple doses. Loratadine (n = 60) or placebo (n = 61) was given once daily for 15 days to children with a history of allergic rhinitis or chronic idiopathic urticaria. In the loratadine group, 27 boys and 33 girls (52 white, 8 black) were enrolled, with a mean age +/- SD of 3.67 +/- 1.13 years and a mean weight +/- SD of 17.2 +/- 3.8 kg. In the placebo group, 27 boys and 34 girls (53 white, 7 black, 1 Asian) were enrolled, with a mean age +/- SD of 3.52 +/- 1.12 years and a mean weight +/- SD of 17.3 +/- 2.9 kg. Tolerability was assessed based on electrocardiographic results, occurrence of adverse events, changes in vital signs, and results of laboratory tests and physical examinations.


RESULTS
The peak plasma concentrations of loratadine and desloratadine were 7.78 and 5.09 ng/mL, respectively, observed 1.17 and 2.33 hours after administration of loratadine; the areas under the plasma concentration-time curve to the last quantifiable time point for loratadine and desloratadine were 16.7 and 87.2 ng x h/mL, respectively. Single and multiple doses were well tolerated, with no adverse events occurring with greater frequency after multiple doses of loratadine than after placebo. Electrocardiographic parameters were not altered by loratadine compared with placebo. There were no clinically meaningful changes in other tolerability assessments.


CONCLUSIONS
Loratadine was well tolerated in this small, selected group of children aged 2 to 5 years at a dose providing exposure similar to that with the adult dose (ie, 10 mg once daily).
Salmun
L M
LM
Allergy/Respiratory Diseases Clinical Research, Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539, USA. luis.salmun@spcorp.com
Herron
J M
JM
Banfield
C
C
Padhi
D
D
Lorber
R
R
Affrime
M B
MB
D018926:Anti-Allergic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002675:Child, Preschool; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006634:Histamine H1 Antagonists / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D017336:Loratadine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D010592:Pharmaceutic Aids; D010919:Placebos; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D014581:Urticaria / Q000097:blood / Q000188:drug therapy / Q000378:metabolism
D018926:Anti-Allergic Agents; D006634:Histamine H1 Antagonists; D010592:Pharmaceutic Aids; D010919:Placebos; D017336:Loratadine; C121345:desloratadine