PMID- 17697908
OWN - NLM
STAT- MEDLINE
DCOM- 20070905
LR  - 20180312
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 5
DP  - 2007 May
TI  - Influence of food on the oral bioavailability of rupatadine tablets in healthy 
      volunteers: a single-dose, randomized, open-label, two-way crossover study.
PG  - 900-908
LID - S0149-2918(07)00133-6 [pii]
LID - 10.1016/j.clinthera.2007.05.004 [doi]
AB  - BACKGROUND: Rupatadine is an oral active antihistamine for the management of 
      diseases with allergic inflammatory conditions, such as perennial and seasonal 
      rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for 
      the treatment of allergic rhinitis and chronic urticaria in adults and 
      adolescents in several European countries. OBJECTIVE: The purpose of this study 
      was to describe the effect of the concomitant intake of food on the 
      pharmacokinetic profile and bioavailability of a single dose of rupatadine. 
      METHODS: This was a single-dose, randomized, open-label, 2-way crossover study in 
      which healthy male and female volunteers received a single, 20-mg oral dose of 
      rupatadine under fed and fasting conditions. Blood samples were collected and 
      plasma concentrations of rupatadine and its active metabolites desloratadine and 
      3-hydroxydesloratadine were determined by liquid chromatography tandem mass 
      spectrometry. Tolerability was based on the recording of adverse events (AEs), 
      physical examinations, electrocardiograms, and laboratory tolerability tests 
      immediately before each treatment period and at the final visit of the study. 
      RESULTS: Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years 
      [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 
      females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 
      58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal 
      distribution of sex. A significant increase in AUC from drug administration to 
      the final quantifiable sample (AUC(0-t)) and AUC from drug administration to 
      infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions 
      without affecting C(max). The ratios (90% CI) of the mean log-transformed 
      AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in 
      AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 
      113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). 
      Plasma concentration-time profiles of desloratadine and 3-hydroxydesloratadine 
      were similar with and without food, and no differences were seen for AUC(0-t), 
      AUC(0-infinity), or C(max). Seven (28%) subjects reported > or =1 AE. All AEs 
      were mild, resolved spontaneously, and did not affect the outcome of the study. 
      CONCLUSIONS: The results of this study indicate that concomitant intake of food 
      with a single 20-mg oral dose of rupatadine exhibits a significant increase in 
      rupatadine bioavailability. Despite the absence of bioequivalence, the drug was 
      well tolerated under fed and fasting conditions, and no major changes in severity 
      and/or prevalence of AEs were reported.
FAU - Solans, Anna
AU  - Solans A
AD  - Pharmacokinetic and Bioanalysis Department, J Uriach y Compania, S.A., Barcelona, 
      Spain. Electronic address: pk-asolans@uriach.com.
FAU - Carbo, Marcel Li
AU  - Carbo ML
AD  - Pharmacokinetic and Bioanalysis Department, J Uriach y Compania, S.A., Barcelona, 
      Spain.
FAU - Pena, Juana
AU  - Pena J
AD  - Pharmacokinetic and Bioanalysis Department, J Uriach y Compania, S.A., Barcelona, 
      Spain.
FAU - Nadal, Teresa
AU  - Nadal T
AD  - Pharmacokinetic and Bioanalysis Department, J Uriach y Compania, S.A., Barcelona, 
      Spain.
FAU - Izquierdo, Inaki
AU  - Izquierdo I
AD  - Clinical Research Unit, J Uriach y Compania, S.A., Barcelona, Spain.
FAU - Merlos, Manuel
AU  - Merlos M
AD  - Drug Development, J Uriach y Compania, S.A., Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Histamine H1 Antagonists)
RN  - 0 (Tablets)
RN  - 2AE8M83G3E (rupatadine)
RN  - 2YHB6175DO (Cyproheptadine)
RN  - 3H9FFN759V (3-hydroxydesloratadine)
RN  - 7AJO3BO7QN (Loratadine)
RN  - FVF865388R (desloratadine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Cyproheptadine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - *Food-Drug Interactions
MH  - Histamine H1 Antagonists/administration & dosage/*pharmacokinetics
MH  - Humans
MH  - Loratadine/analogs & derivatives/blood/pharmacokinetics
MH  - Male
MH  - Tablets
EDAT- 2007/08/19 09:00
MHDA- 2007/09/06 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/03/02 00:00 [accepted]
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/09/06 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - S0149-2918(07)00133-6 [pii]
AID - 10.1016/j.clinthera.2007.05.004 [doi]
PST - ppublish
SO  - Clin Ther. 2007 May;29(5):900-908. doi: 10.1016/j.clinthera.2007.05.004.