Trial reportEuropean journal of clinical pharmacology2007
Tolfenamic acid is a potent CYP1A2 inhibitor in vitro but does not interact in vivo: correction for protein binding is needed for data interpretation.
Trial report in European journal of clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed, 13 citations in OpenAlex.
- Celecoxib is a CYP1A2 inhibitor in vitro but not in vivo.European journal of clinical pharmacology · 2008Trial
- Article
- Quantitative Prediction of Drug Interactions Caused by CYP1A2 Inhibitors and Inducers.Clinical pharmacokinetics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveOur aim was to correlate the in vitro and in vivo CYP1A2 inhibition potential of tolfenamic acid, an NSAID highly (99.7%) bound to plasma proteins, to study the significance of protein binding of inhibitor in metabolic drug interactions.
methodsThe effect of tolfenamic acid on CYP1A2 (phenacetin O-deethylation) was studied using human liver microsomes, with and without albumin (0-10 mg/ml). In a randomized, crossover study, 10 volunteers took 200 mg tolfenamic acid or placebo t.i.d. for 3 days. On day 2, a caffeine test was performed. On day 3, each ingested 4 mg of the CYP1A2 substrate tizanidine. Plasma tizanidine, its metabolites (M) and tolfenamic acid, and pharmacodynamic variables were measured.
resultsTolfenamic acid strongly inhibited phenacetin-O-deethylation in vitro (IC(50) 1.8 microM without albumin). Albumin decreased its inhibitory effect in a concentration-dependent manner; the IC(50) exceeded 100 microM with 10 mg/ml of albumin. Tolfenamic acid had no effect on the area under the concentration-time curve (AUC(0-oo)), peak concentration, time of peak concentration or half-life of tizanidine or M-3; only the AUC(0-oo) of secondary metabolite M-4 was slightly decreased (13%, P = 0.004). The caffeine test and the pharmacodynamic effects of tizanidine were unchanged.
conclusionsTolfenamic acid potently inhibits CYP1A2 in vitro when studied without albumin, but not in vivo. This apparent discrepancy is due to the high protein binding of tolfenamic acid. To avoid overestimation of the interaction potential, the inhibitory effect of highly albumin-bound compounds should also be studied in vitro with albumin, or their exact unbound plasma concentration should be used in predictions.
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