Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent

@article{Pentikinen2004HumanPO,
  title={Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent},
  author={Pertti J. Pentik{\"a}inen and Pertti J. Neuvonen and C. Backman},
  journal={European Journal of Clinical Pharmacology},
  year={2004},
  volume={19},
  pages={359-365}
}
SummaryThe pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (Vdβ) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h… 
Pharmacokinetics of tolfenamic acid: Disposition in bile, blood and urine after intravenous administration to man
TLDR
To study its pharmacokinetics and especially its biliary excretion, 14C-tolfenamic acid was infused i.v. in patients with a T-tube inserted in the common bile duct at choledocholithotomy 7–10 days prior to the study.
Pharmacokinetics of tolfenamic acid in patients with cirrhosis of the liver
TLDR
There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis, and there was good correlation between individual elimination rate constants or plasma clearances with the liver function tests, serum albumin and P-coagulation factors.
Effect of moxifloxacin administration on pharmacokinetics of tolfenamic acid in rats
TLDR
Concomitant administration of moxifloxacin may alter the disposition of tolfenamic acid in male rats and the peak plasma drug concentration was significantly higher in female rats compared to male rats.
Influence of marbofloxacin on the pharmacokinetics and pharmacodynamics of tolfenamic acid in calves.
TLDR
The pharmacodynamic properties of TA were not influenced by MB co-administration, in spite of the alterations in some TA pharmacokinetic parameters, and provide a basis for the rational use of TA in combination with MB in calf medicine.
Pharmacokinetics of tolfenamic acid following two oral dose levels in buffalo calves.
TLDR
The dosage levels of tolfenamic acid employed in the present study were comparable with the doses used by previous workers in calves, dogs, rats, and human beings, but its pharmacokinetic data are not available in buffalo species.
Effect of magnesium hydroxide on the absorption of tolfenamic and mefenamic acids
TLDR
Concomitant ingestion of the fenamates with an antacid preparation containing both aluminium and magnesium hydroxides, or water alone were ingested with tolfenamic acid 400 mg, and the effect of various antacids on the absorption of tolfanamic and mefenamic acids was investigated.
Tolfenamic acid is a potent CYP1A2 inhibitor in vitro but does not interact in vivo: correction for protein binding is needed for data interpretation
TLDR
Tolfenamic 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.
Protein binding of tolfenamic acid in the plasma from patients with renal and hepatic disease
TLDR
Measurements of binding properties in whole blood and blood cell — buffer suspension showed that tolfenamic acid interacts with the lipid membrane structures of blood cells, while salicylic acid is distributed into the aqueous cell space.
Orally administered tolfenamic acid inhibits leukotriene synthesis in isolated human peripheral polymorphonuclear leukocytes
TLDR
It is suggested that inhibition of leukotriene synthesis is an additional mechanism of the anti-inflammatory, antimigraine and antidysmenorrhoeic effects of tolfenamic acid, and a possible explanation for its rare gastric and bronchoconstrictive side-effects.
...
...

References

SHOWING 1-10 OF 23 REFERENCES
The pharmacokinetics of diclofenac sodium following intravenous and oral administration
TLDR
The pharmacokinetics of diclofenac were examined following single rapid intravenous injection and also following single oral doses to healthy female volunteers, finding that Fifty percent of orally dosed dic lofenacs did not reach the systemic circulation due, predominantly, to first-pass metabolism.
Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment.
TLDR
The two-compartmental open-system model is discussed in respect to the error introduced into the usual absorption rate and elimination rate calculations and on the estimation of the volume of distribution of various drugs.
Prolonged treatment with tolfenamic acid in inflammatory rheumatic diseases.
TLDR
The clinical effect was found to be good, and tolfenamic acid appeared to be well suited for long-term symptomatic treatment of rheumatics.
Assessment of pharmacokinetic constants from postinfusion blood curves obtained after I.V. infusion.
TLDR
A mathematical equation is presented which enables one to determine the parameters identical to an i.v. bolus injection curve by utilizing the postinfusion blood curve, applicable to all compartmental models that may be described by linear first-order differential equations with constant coefficients.
New method for calculating the intrinsic absorption rate of drugs.
TLDR
It is shown that methods based on the single-compartment concept do not result in acceptable estimates of the absorption rates, and a new equation is presented, presuming the drug distributes between a central and one peripheral compartment, which results in an accurate estimate of the known rates of infusion (absorption) for the drugs studied to date.
Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro.
The effect of tolfenamic acid on prostaglandin biosynthesis was investigated by using rabbit kidney medulla microsomal fraction, and the results compared with those obtained with indomethacin and
Age differences in drug binding by plasma proteins: Studies on human foetuses, neonates and adults
TLDR
The binding to human plasma proteins of ampicillin, α-azidobenzylpenicillin, benzylpeniillin, phenobarbital and diphenylhydantoin was studied by equilibrium dialysis of labelled compounds to determine the age dependence of drug binding activity.
Bioavailability--a problem in equivalence.
TLDR
Some statistical aspects of bioavailability are presented, which include the statistical considerations for designing and analyzing bioavailability studies, and various statistical approaches listed.
Effect of the common bile acids on the fibrin/fibrinogen fragments in rheumatoid synovial fluid. A possible clue to the ameliorating effect of jaundice in rheumatoid arthritis.
TLDR
The influence of the common bile acids on the plasmin digestion of these degradation products in 16 rheumatoid synovial fluids were quantitated immunologically by radial immunodiffusion, and qualitatively estimated by crossed immunoelectrophoresis.
...
...