Antihistaminic effects of rupatadine and PKPD modelling.
Rupatadine is a new oral antihistaminic agent used for the management of allergic inflammatory conditions, such as rhinitis and chronic urticaria. The aim of the present study was to develop a population pharmacokinetic/pharmacodynamic (PKPD) model for the description of the effect of rupatadine and one of its active metabolites, desloratadine, on the histamine-induced flare reaction and to predict the response to treatment after repeated administrations of rupatadine. Both rupatadine and desloratadine were characterized by two-compartmental kinetics. For both compounds, covariates sex and weight had a significant effect on several parameters. The pharmacodynamics were described by an indirect model for the inhibition of flare formation that accounted for the contribution of both rupatadine and desloratadine to the antihistaminic effect. The final PKPD model adequately described the original data. The simulated response after repeated once-daily administrations of 10 mg rupatadine showed a significant and maintained antihistaminic effect over time, between two consecutive dosing intervals.
Peña
Juana
J
Pharmacokinetic & Bioanalysis Department, Palau Pharma SA, Barcelona, Spain.
Carbo
Marcel Li
ML
Solans
Anna
A
Nadal
Teresa
T
Izquierdo
Iñaki
I
Merlos
Manuel
M
D000328:Adult; D000465:Algorithms; D001711:Biotransformation; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006633:Histamine Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D017336:Loratadine / Q000097:blood; D008297:Male; D015233:Models, Statistical; D011153:Population; D012737:Sex Factors
D006633:Histamine Antagonists; C103639:rupatadine; D003533:Cyproheptadine; D017336:Loratadine
J Investig Allergol Clin Immunol. 2005;15(1):22-9
15864879
Ann Allergy Asthma Immunol. 2006 Jan;96(1):37-44
16440531
J Investig Allergol Clin Immunol. 2004;14(1):34-40
15160440
Drugs. 2007;67(3):457-74
17335300
Allergy. 2004 Jul;59(7):766-71
15180765
J Pharmacol Exp Ther. 1997 Jan;280(1):114-21
8996188
Allergy Asthma Proc. 2000 May-Jun;21(3):135-40
10892514
Clin Pharmacokinet. 1995 May;28(5):419-32
7614779
Clin Pharmacol Ther. 2000 Dec;68(6):647-57
11180025
Drugs. 1999 Jan;57(1):31-47
9951950
Neuropsychobiology. 2004;50(4):311-21
15539863
Nephron. 1976;16(1):31-41
1244564
Int J Clin Pharmacol Ther. 1999 Oct;37(10):499-502
10543317