Replies to post #49103 on Biotech Values

[dewophile]

"It only makes sense that drugs that affect the nasal mucosa, such as topical nasal decongestants, would affect the absorption of an intranasal drug. And speaking as someone who is getting over a cold, I'd expect that the abundant mucus I produced would also interfere with absorption."


I'm not so sure about this. I had to use synarel recently in a patient allergic to lupron and I know no dose adjustment is necessary for rhinitis. So even though it may seem intuitive that congestion and a runny nose can affect nasal clearance, and drug interactions may exist when certain classes of drugs such as vasoconstrictors are used, I have a hunch the clinical effect is negligible...I'll do some digging on the subject and post if I find anything relevent

PS: feel better!

[dewophile]

JAV
Good review of nasal drug delivery physiology

Nasal Clearance in Health and Disease
LISBETH ILLUM, Ph.D., D.Sc.

It is subscription only so I cannot post the whole article, but here is a relevant excerpt:

"It was found early
on that an experimentally induced rhinitis had little
effect on the luteinising hormone response in
human volunteers that were administered buserelin
nasally.18 It was concluded in the study that
any modifications to the dosage schedule or delivery
route was unnecessary during natural nasal
inflammations, such as common cold and allergic
rhinitis. Similarly, studies on thyroid stimulating
hormone19 and desmopressin20 both demonstrated
no difference in absorption in healthy subjects
and in subjects suffering from common colds
or rhinitis. In a comparative study between the
nasal absorption of triamcinolone acetonide in
healthy volunteers and in patients with allergic
rhinitis no difference in absorption was seen.21
Similar experiments were performed for ipratropium
bromide and dihydroergotamine and the
results showed no difference in pharmacokinetic
parameters between healthy volunteers and volunteers
with rhinitis or common colds.22,23 It is
reasonable to conclude that although rhinitis and
common colds have been shown to have an effect
on nasal clearance there has been no indication
from the studies performed and discussed above
that such diseases would have an effect on the
nasal absorption of drugs."

[Bio_pete]

Jav- I'm invested in POZN so I've done a fair amount of research into the FDA's position concerning NSAID's. I posted an article last night which mentions the cardiovascular risks associated with Voltaren,(Diclofenac) .

"On the other hand, high doses of Advil (800 mg three times a day) and Voltaren (75 mg twice daily) were associated with rates of heart attack that were 51 percent and 63 percent higher, respectively, than placebo. An analysis of a large number of trials comparing COX-2 inhibitors to other NSAIDs found similar results – that Voltaren was estimated to increase vascular risk by about 70 percent over Aleve".
http://www.seniorjournal.com/NEWS/Health/2007/7-04-25-FDACauses.htm

Javelins management has stated that they don't foresee any safety challenges before the FDA for Dyloject, but I'm not as confident. Does the cardiovascular risks associated with Diclofenac concern you?