Tenidap- An anti-inflammatory cytokine inhibitor - Investigational Drugs
Drug Name:Tenidap- An anti-inflammatory cytokine inhibitor - Investigational Drugs
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Rheumatoid arthritis
Summary-
Studies conducted to date, both in vitro and in vivo, clearly suggest that tenidap is a
unique anti-rheumatoid agent with disease modifying potential. Based on clinical and
laboratory parameters, tenidap is more efficacious than NSAIDs and comparable to
current mainstay of RA therapy.
Tenidap appears to hold promise as a major new drug in the management of rheumatoid
arthritis and osteoarthritis.
Pfizer filed an NDA with FDA for tenidap on December 22, 1993. It will be available
as Enable
Adverse Reaction:
Side effects-
The most significant side effects reported in tenidap clinical trials has been reversible
proteinuria of proximal tubular origin , occuring in < 20% of patients. This has not been
associated with renal function impairment. One study reported 24% GI side effects in
patients receiving tenidap
Pharmacology/ Pharmacokinetics:
Pharmacology-
Tenidap sodium is an anti-inflammatory agent developed agent being developed
for use in the treatment of rheumatoid arthritis and osteoarthritis. Whereas NSAIDs
decrease postaglandin synthesis by inhibiting cyclogenase , tenidap appears to
inhibit both cyclogenase and -lipoxygenase, thus impairing production of both
postaglandin and leukotrienes
Although exact mechanism of action has not been established, in vitro studies suggest
that tenicap lowers concentrations of interleukin-1, interlekin -6 ,leukotrine B4 , tumor
necrosis factor and C-reactive proteins. It also inhibits the release of neutrophil
collagenase.
Tthe arachoidonic acid metabolites inhibited by tenidap are potent anti-inflammatory
mediators that profoundly augument leukocytes chemotaxis. The failure of NSAIDs
to inihibit the lipogenase pathway partially explains their inability to significantly
alter the progressive tissue destruction often associated with rheumatoid arthritis.
Thus the unique pharmacology of tenidap provides the drug with a distinct
pharmacologic advantage over NSAIDs
Pharmacokinetics-
Todate, pharmacokinetic data on tenidap has not been published. It is known that
the drug is roughly 99% recersibly bound to albumin, and multiple dosing
of 120mg/day yields a serum concentration of approximately 5 to 15mg/L
Clinical trials-
A recent report describes four separate studies comparing tenidap to naproxen
( Naprosyn) or placebo in treating rheumatoid arthritis (RA) . Doses of tenidap
ranged from 40 to 120mg/day , naproxen dosage was 500mg twice daily.
Patients were allowed to remain on other medications, such as auranafin (Ridaura)
penicillamine (Cuprimine, Depen). hydroxychloroquine (Plaquernil Sulfate ) and
prednisolone ( Deltasone) . Durations ranged from 2 weeks to 1 year.
All four studies demonostrated a significantly greater reduction in C-reactive protein
with tanidap than naproxen or placebo.
In another study 374 volunteers with RA treated previously with only NSAIDs
were randomised to ether receive tenidap 120mg/day or auranofin 3mg twice daily
with diclofenac (Cataflam, Voltaren) 50mg 3 times daily. Evaluation included patient
and physician assessment of disease activity, number of painful joints, swollen joints,
and pain. After 9 months there was no significant differences between the two therapies,
though a higher rate of discontinuation was reported for aurnofin due to diarrhea.
A similar trial involving 367 patients compared 120mg/day of tenidap to piroxicam
(Feldene ) 20mg/day alone, and in combination with hydroxchloroquine 400mg/day
for 2 years.. Based on clinical evaluation, results indicated that tenidap therapy
was more effective than piroxicam and equally as effective as combination of
piroxicam and hydrochoroquine
A 1 year multi-center study of 488 RA patients compared clinical efficacy of
tratment with 40,80,120mg/day tenidap to treatment with 500, 750 or 1000mg/day
naproxen beginning with the lowest dose and titrating to clinical response.
Efficacy of the two treatments, was not significantly different during the first
4 weeks, but tenidap became significantly more efficacious by 24 weeks.
Reductions in all acute phase reactants were significantly greater in the
tenidap- treated group.
