Pimecrolimus More Skin Specific Than Tacrolimus

[Guest guest]

Hi,

I know some of you are using Pimecrolimus for your seb derm. Here's a

brief article on it that I found in the March 2002 issue of Skin and

Allergy News.

Take care,

Matija

Doesn't penetrate skin as readily

Pimecrolimus More Skin Specific Than Tacrolimus

F. Kirn

Sacramento Bureau

MAUI, HAWAII — Tacrolimus may be a more potent agent, but

pimecrolimus is more skin specific because it does not penetrate

through the skin as readily, Dr. Abrams said at the annual

Hawaii dermatology seminar sponsored by the Skin Disease Education

Foundation.

Studies conducted by the manufacturer of Elidel (pimecrolimus 1%)

suggest that 92% of the drug stays in the skin applied, said Dr.

Abrams, director of medical affairs for Novartis

Pharmaceuticals Corp, East Hanover, N.J. Even in patients who have

been treated over 90% of their body area, the highest blood levels of

the drug that have been measured have been 2 ng/mL, which is not even

high enough to determine how and where it is metabolized

systemically.

Other studies have found that pimecrolimus is demethylated in the

liver and excreted in the feces.

In psoriasis studies, the drug has been given orally and it has been

shown that at blood levels almost 250 times higher there is no

toxicity, he said.

Comparing the two topical immunomodulators approved for the treatment

of atopic dermatitis, Dr. Abrams said that pimecrolimus is the more

lipophilic of the two. Therefore, it penetrates the skin more slowly

and most of it stays there.

In testing pimecrolimus, the company used mouse and rat models of

allergic contact dermatitis, kidney transplant, and graft-versus-host

disease. They found in the contact dermatitis model that tacrolimus

was 10 times more potent than cyclosporine, while pimecrolimus was 2-

4 times more potent than cyclosporine.

However, because pimecrolimus has greater affinity for the skin, the

amount of tacrolimus delivered to the lymph nodes was 10 times higher

than the amount of pimecrolimus.

When they looked at sensitization to allergic contact dermatitis,

they found that tacrolimus was able to prevent sensitization while

pimecrolimus was not, Dr. Abrams said. But there was no difference in

effect in the animals already sensitized.

Previous comparisons have suggested that in atopic dermatitis,

tacrolimus may be more effective but may also be associated with more

discomfort—a burning sensation on application—than pimecrolimus (SKIN

& ALLERGY NEWS, November 2001, p. 26).

Studies undertaken in both pig skin and human subjects have

demonstrated that there is no skin atrophy caused by long-term use of

pimecrolimus, and that even when used for 12 months there appears to

be no systemic accumulation, Dr. Abrams said.

[Guest guest]

.... ...

> Studies conducted by the manufacturer of Elidel (pimecrolimus 1%)

> suggest that 92% of the drug stays in the skin applied, said Dr.

> Abrams, director of medical affairs for Novartis

> Pharmaceuticals Corp, East Hanover, N.J. Even in patients who have

> been treated over 90% of their body area, the highest blood levels

> of the drug that have been measured have been 2 ng/mL, which is not

> even high enough to determine how and where it is metabolized

> systemically....

It's great that information on new drugs gets shared for everyone to

see.

It looks like this article comes from a lecture given by the drug

company, and quotes from studies conducted by the company itself.

Most physicians would view this with some skepticism, knowing that

drug companies can and do design their studies to showcase their drug

to best effect, and it's understood they will spin the stats as best

they can. Many would wait for these statements to be independently

verified before incorporating this information into patient care.

Marjorie

Marjorie Lazoff, MD

> Other studies have found that pimecrolimus is demethylated in the

> liver and excreted in the feces.

>

> In psoriasis studies, the drug has been given orally and it has

been

> shown that at blood levels almost 250 times higher there is no

> toxicity, he said.

>

> Comparing the two topical immunomodulators approved for the

treatment

> of atopic dermatitis, Dr. Abrams said that pimecrolimus is the more

> lipophilic of the two. Therefore, it penetrates the skin more

slowly

> and most of it stays there.

>

> In testing pimecrolimus, the company used mouse and rat models of

> allergic contact dermatitis, kidney transplant, and graft-versus-

host

> disease. They found in the contact dermatitis model that tacrolimus

> was 10 times more potent than cyclosporine, while pimecrolimus was

2-

> 4 times more potent than cyclosporine.

>

> However, because pimecrolimus has greater affinity for the skin,

the

> amount of tacrolimus delivered to the lymph nodes was 10 times

higher

> than the amount of pimecrolimus.

>

> When they looked at sensitization to allergic contact dermatitis,

> they found that tacrolimus was able to prevent sensitization while

> pimecrolimus was not, Dr. Abrams said. But there was no difference

in

> effect in the animals already sensitized.

>

> Previous comparisons have suggested that in atopic dermatitis,

> tacrolimus may be more effective but may also be associated with

more

> discomfort—a burning sensation on application—than pimecrolimus

(SKIN

> & ALLERGY NEWS, November 2001, p. 26).

>

> Studies undertaken in both pig skin and human subjects have

> demonstrated that there is no skin atrophy caused by long-term use

of

> pimecrolimus, and that even when used for 12 months there appears

to

> be no systemic accumulation, Dr. Abrams said.

[Guest guest]

.... ...

> Studies conducted by the manufacturer of Elidel (pimecrolimus 1%)

> suggest that 92% of the drug stays in the skin applied, said Dr.

> Abrams, director of medical affairs for Novartis

> Pharmaceuticals Corp, East Hanover, N.J. Even in patients who have

> been treated over 90% of their body area, the highest blood levels

> of the drug that have been measured have been 2 ng/mL, which is not

> even high enough to determine how and where it is metabolized

> systemically....

It's great that information on new drugs gets shared for everyone to

see.

It looks like this article comes from a lecture given by the drug

company, and quotes from studies conducted by the company itself.

Most physicians would view this with some skepticism, knowing that

drug companies can and do design their studies to showcase their drug

to best effect, and it's understood they will spin the stats as best

they can. Many would wait for these statements to be independently

verified before incorporating this information into patient care.

Marjorie

Marjorie Lazoff, MD

> Other studies have found that pimecrolimus is demethylated in the

> liver and excreted in the feces.

>

> In psoriasis studies, the drug has been given orally and it has

been

> shown that at blood levels almost 250 times higher there is no

> toxicity, he said.

>

> Comparing the two topical immunomodulators approved for the

treatment

> of atopic dermatitis, Dr. Abrams said that pimecrolimus is the more

> lipophilic of the two. Therefore, it penetrates the skin more

slowly

> and most of it stays there.

>

> In testing pimecrolimus, the company used mouse and rat models of

> allergic contact dermatitis, kidney transplant, and graft-versus-

host

> disease. They found in the contact dermatitis model that tacrolimus

> was 10 times more potent than cyclosporine, while pimecrolimus was

2-

> 4 times more potent than cyclosporine.

>

> However, because pimecrolimus has greater affinity for the skin,

the

> amount of tacrolimus delivered to the lymph nodes was 10 times

higher

> than the amount of pimecrolimus.

>

> When they looked at sensitization to allergic contact dermatitis,

> they found that tacrolimus was able to prevent sensitization while

> pimecrolimus was not, Dr. Abrams said. But there was no difference

in

> effect in the animals already sensitized.

>

> Previous comparisons have suggested that in atopic dermatitis,

> tacrolimus may be more effective but may also be associated with

more

> discomfort—a burning sensation on application—than pimecrolimus

(SKIN

> & ALLERGY NEWS, November 2001, p. 26).

>

> Studies undertaken in both pig skin and human subjects have

> demonstrated that there is no skin atrophy caused by long-term use

of

> pimecrolimus, and that even when used for 12 months there appears

to

> be no systemic accumulation, Dr. Abrams said.