A retrospective, open-label analysis of the population pharmacokinetics of a single 10-mg dose of loratadine in healthy white Jordanian male volunteers.
BACKGROUND
Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H(1)-receptor antagonist activity. Loratadine 10-mg tablets have been reported to be rapidly absorbed after once-daily administration for 10 days in healthy adult subjects, with a T(max) of 1.3 hours for loratadine and 2.5 hours for its major active metabolite, descarboethoxyloratadine. The t(1/2) in normal adult subjects has been reported to be 8.4 hours (range, 3-20 hours) for loratadine and 28 hours for its metabolite.


OBJECTIVE
The aim of this study was to determine the population pharmacokinetics of loratadine after oral administration.


METHODS
A retrospective analysis was conducted of prior noncompartmental analysis results from healthy white Jordanian male subjects who participated in 2 pharmacokinetic studies. After a 10-hour overnight fast, a single 10-mg loratadine tablet was administered orally followed by 240 mL of water. Blood samples were collected before dosing and at 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours after dosing. Mean and population plasma level profiles were examined. The calculated primary and secondary pharmacokinetic parameters were V(d)/F, k(e), absorption rate constant, lag time, distribution rate constant, redistribution rate constant, T(max), and C(max).


RESULTS
A total of 72 healthy male subjects with a mean (SD) age of 23 (3.57) years participated in the 2 studies. The analytical method was linear over the concentration range from 0.10 to 20.00 ng/mL (r > 0.999). The lower limit of quantitation was 0.1 ng/mL with 95% accuracy. Precision, expressed as %CV, was 7.44%. Intraday accuracy ranged from 91.9% to 97.2% at high and low quality control levels, respectively. Interday accuracy ranged from 93.57% (%CV, 4.35%) to 98.78% (%CV, 5.78%), respectively. Population ke, t(1/2), absorption rate constant, and absorption t(1/2) were 0.19 hour(-1), 3.65 hours, 1.31 hours(-1), and 0.53 hour, respectively. Distribution rate constant, redistribution rate constant, and lag time were 0.31 hour(-1), 0.02 hour(-1), and 0.32 hour, respectively. The noncompartmental estimate for C(max) was 3.02 ng/mL, which occurred at 1.30 hours, with a t(1/2) of 5 hours and a k(e) of 0.14 hour(-1). No adverse events were recorded during the study.


CONCLUSIONS
The population t(1/2) for loratadine was 3.65 hours in this group of healthy white Jordanian male volunteers, shorter than that observed in previous research.
Salem
Isam I
II
International Pharmaceutical Research Center, Amman, Jordan. dr.salem@iprc.com.jo
Najib
Naji M
NM
Idkaidek
Nasir M
NM
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D006207:Half-Life; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007597:Jordan; D017336:Loratadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D012189:Retrospective Studies; D013607:Tablets; D053719:Tandem Mass Spectrometry; D044465:White People; D055815:Young Adult
D039563:Histamine H1 Antagonists, Non-Sedating; D013607:Tablets; D017336:Loratadine