PMID- 20184225
OWN - NLM
STAT- MEDLINE
DCOM- 20100322
LR  - 20121115
IS  - 0004-4172 (Print)
IS  - 0004-4172 (Linking)
VI  - 60
IP  - 1
DP  - 2010
TI  - Comparative bioavailability study of triflusal oral solution vs. triflusal 
      capsules in healthy subjects. A single, randomized, two-way cross-over, 
      open-label phase I study.
PG  - 36-41
LID - 10.1055/s-0031-1296246 [doi]
AB  - Triflusal (CAS 322-79-2) is an antiplatelet agent that irreversibly acetylates 
      cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. 
      The main metabolite of triflusal, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), 
      possesses also antiaggregant activity. Recently a new oral 600 mg (10 ml) 
      solution form of triflusal has been developed. The purpose of this clinical trial 
      was to study the relative bioavailability of the new oral solution of triflusal 
      versus the capsules formulation, both administered as a single dose. This was a 
      randomized, two-way, cross-over, open-label, single-site phase I clinical trial, 
      in 24 healthy volunteers who received triflusal as 600 mg oral solution and as 
      two 300 mg capsules in a single administration separated by a washout period of 
      at least 17 days. Blood samples were collected and plasma concentrations of HTB 
      were measured. Pharmacokinetic parameters used for bioequivalence assessment 
      included AUC(0-t), AUC(0-inf) and Cmax. The formulations were considered 
      bioequivalent if the geometric mean ratios of AUC(0-t), AUC(0-inf) and Cmax were 
      within the predetermined equivalence range (80% to 125%). Tolerability was based 
      on the recording of adverse events (AEs), physical examination, electrocardiogram 
      (ECG) and laboratory tests. The parameters for bioequivalence, mean [SD] values 
      were as follows: AUC(0-t) (microg x h/ml): 3574.08 [628.17] for triflusal oral 
      solution and 3901.78 [698.43] for triflusal capsules; AUC(0-infinity) (microg x 
      h/ml): 4089.21 [842.54] for triflusal oral solution and 4471.33 [905.93] for 
      triflusal capsules; Cmax, (microg/ml): 91.24 [12.88] for triflusal oral solution 
      and 88.61 [13.46] for triflusal capsules; Cmax/AUC(0-infinity) (h(-1)): 0.03 
      (0.00) for triflusal oral solution and 0.02 (0.00) for triflusal capsules. The 
      90% confidence intervals for the ratio experimental/control by analysis of 
      variance after log transformed AUC(0-infinity), AUC(0-t), and Cmax were within 
      80% to 125%. Similar results were found for the data without log transformation. 
      All adverse events were of mild or moderate intensity and all subjects recovered. 
      Nine and 12 subjects reported at least one adverse event during treatment with 
      triflusal oral solution and with triflusal capsules, respectively. The most 
      frequently reported adverse events were headache and dizziness. It was concluded 
      that the 600-mg solution of triflusal appeared to be bioequivalent to the 
      reference formulation capsules. Both formulations were well tolerated.
FAU - Izquierdo, Inaki
AU  - Izquierdo I
AD  - Clinical Development Unit, J. Uriach y Compania, S.A., Barcelona, Spain. 
      clin-izquierdo@uriach.com
FAU - Borja, Javier
AU  - Borja J
FAU - Rovira, Sandra
AU  - Rovira S
FAU - Pelagio, Pilar
AU  - Pelagio P
FAU - Torres, Ferran
AU  - Torres F
FAU - Cebrecos, Jesus
AU  - Cebrecos J
FAU - Garcia-Rafanell, Julian
AU  - Garcia-Rafanell J
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Arzneimittelforschung
JT  - Arzneimittel-Forschung
JID - 0372660
RN  - 0 (Capsules)
RN  - 0 (Pharmaceutical Solutions)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Salicylates)
RN  - 1Z0YFI05OO (triflusal)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Biological Availability
MH  - Capsules
MH  - Chemistry, Pharmaceutical
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Male
MH  - Pharmaceutical Solutions
MH  - Platelet Aggregation Inhibitors/*administration & dosage/*pharmacokinetics
MH  - Salicylates/*administration & dosage/*pharmacokinetics
MH  - Young Adult
EDAT- 2010/02/27 06:00
MHDA- 2010/03/23 06:00
CRDT- 2010/02/27 06:00
PHST- 2010/02/27 06:00 [entrez]
PHST- 2010/02/27 06:00 [pubmed]
PHST- 2010/03/23 06:00 [medline]
AID - 10.1055/s-0031-1296246 [doi]
PST - ppublish
SO  - Arzneimittelforschung. 2010;60(1):36-41. doi: 10.1055/s-0031-1296246.