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Q: topical treatments for psoriasis *FOR TEHUTI* ( Answered 5 out of 5 stars,   0 Comments )
Subject: topical treatments for psoriasis *FOR TEHUTI*
Category: Health > Medicine
Asked by: tom136-ga
List Price: $30.00
Posted: 05 Jun 2003 03:09 PDT
Expires: 05 Jul 2003 03:09 PDT
Question ID: 213316
Dear Tehuti: Would you please answer this question? 
I need a comparision of the following three topical treatments for
1)topical Tacrolimus
2)topical Cyclosporin A
3)topical Calcipotriol + Betamethasone

What I need to know is whether there are some differences between
them, I mean some indication of superiority of one of them over the
others in any respect. I need to rank them in order of potential
superiority or other available variable(s). I think that the above
cited products are still under development. Please, if possible, let
me know whether they are already on the worldwide market (I am only
interested on the topical dosage form). As always, I do not expect a
*perfect* answer. Do what you can (I know that as this is still a
research area, not much information is available yet).
Thanks a lot in advance : )
Subject: Re: topical treatments for psoriasis *FOR TEHUTI*
Answered By: tehuti-ga on 06 Jun 2003 11:59 PDT
Rated:5 out of 5 stars
Hello Tom,

Thank you for your patience on this question.  As you say, there is
not that much definite information so far.  To summarise what I have
found (references are listed at the bottom):

Tacrolimus is 10-100 times more potent that cyclosporin in oral use. 
It is also considered to be a better candidate for topical use, due to
its smaller molecular weight and lipophilicity.  Cyclosporin is
generally considered to be ineffective when administered topically.
There is, however, some evidence that cyclosporin could also be
effective when administered topically in oil. Intradermal injections
of cyclosporin into lesions have also been found effective, suggesting
that it is indeed the poor dermal absorption which accounts for the
poor efficacy of topical cyclosporin. Skin penetration is increased by
electroporation, but most of the cyclosporin remains bound to skin
tissue. Modest efficacy has recently been reported for CGC1072, a
novel hepta-arginine conjugate designed to deliver therapeutic levels
of cyclosporin to the skin.

Topical tacrolimus has been found effective against atopic eczema, but
results in psoriasis trials have been mixed, with some reporting
efficacy and some not. At least one study found it to be as effective
as topical calcipotriol or topical betamethasone (each used
separately), while another study found it to be less effective than
calcipotriol and only as effective as placebo. The use of a liposomal
delivery system increases dermal penetration of tacrolimus, resulting
in higher local concentrations at lesion sites.

A combination of calcipotriol and betamethasone used topically is more
effective than either agent alone. Since the efficacy of topical
tacrolimus has been reported to be similar or less than that of
calcipotriol and betamethasone used separately, and since the
calcipotriol+betamethasone combination is more effective than either
agent alone, it might be reasonable to deduce that the combined C+B
formula is more effective than topical tacrolimus. However, I have not
found any published comparative studies to support or refute this

Against that deduction, however, is the following expert opinion
suggesting that the combined formula does not increase efficacy to a
useful degree:

“The Scottish Medicines Consortium… advises NHS Boards and Area Drug
and Therapeutic Committees (ADTCs) that: Calcipotriol and
betamethasone dipropionate ointment (Dovobet) is not recommended for
general use within the NHS in Scotland as the additional benefits to
accrue over the constituents being applied separately were
insufficient to justify the increased cost involved.”  (NHS Scotland)

With respect to market availability:

A. Calcipotriol/Betamethasone:

Dovobet ointment, LEO Pharmaceuticals  5mcg/g calcipotriol + 0.5 mg/g

Also marketed as Daivobet ointment, eg:

Apr. 02, 2003 
Galen Holdings PLC Enters into Co-Promotion Agreement with
Bristol-Myers Squibb for Dovonex(R) and Licences Dovobet(R) from Leo
Pharma A/S
“Galen is entering into a Development Agreement with LEO Pharma to
develop Dovobet(R), its combination product containing calcipotriene
and betamethasone dipropionate that is currently approved for
marketing by LEO Pharma in certain countries in Europe. LEO Pharma
intends to submit shortly an Investigational New Drug Application
(IND) for Dovobet(R) to the Food and Drug Administration (FDA) in the
US. Both Dovonex(R) and Dovobet(R) are indicated for the treatment of
mild to moderate psoriasis in Europe.
Under the terms of the agreements for Dovobet(R), Galen will pay LEO
Pharma a total of $47 million if Dovobet(R) progresses to full FDA
approval. Of the $47 million, $40 million is payable upon approval.”

B Tacrolimus 

Protopic ointment, Fujisawa Healthcare, 0.03% or 0.1%, “steroid free
alternative for eczema”
European Public Assessment Report (EPAR) (indication is atopic

C  Cyclosporin

I have found only found cyclosporin ointment listed as an ophthalmic
medication, for example:
“RESTASIS (cyclosporine ophthalmic emulsion 0.05%) 
On December 23, 2002, the U.S. Food and Drug Administration (FDA)
approved RESTASIS(™ )(cyclosporine ophthalmic emulsion 0.05%),
developed and manufactured by Allergan, Inc., as the first and only
prescription medication indicated to increase tear production in
patients who don't produce the right amount of tears presumably due to
ocular (eye) inflammation associated with keratoconjunctivitis sicca
(dry eye disease).” (Allergan product)

The novel hepta-arginine cyclosporin conjugate is manufactured by
Cellgate Inc.

The conclusions given above about efficacy are based on the following

1. A pilot study, published in 1998, on the use of topical tacrolimus
in chronic plaque psoriasis, found that its efficacy was no better
than that of placebo, while the efficacy of topical calcipotriol (on
its own) was superior to that of placebo and tacrolimus.

Arch Dermatol 1998 Sep;134(9):1101-2 
Topical tacrolimus is not effective in chronic plaque psoriasis. A
pilot study.
Zonneveld IM, Rubins A, Jablonska S, Dobozy A, Ruzicka T, Kind P,
Dubertret L, Bos JD.
Department of Dermatology, Academisch Medisch Centrum, Amsterdam, The

“… After a washout phase of 2 weeks, patients were randomized to
receive 0.005% calcipotriol ointment twice daily, placebo ointment
once daily, or 0.3% tacrolimus ointment once daily….  The reduction in
the local psoriasis severity index score after 6 weeks was 62.5% in
the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in
the placebo group. CONCLUSIONS: There was no statistically significant
difference between the efficacy of tacrolimus and placebo ointment (P
= .77). Calcipotriol ointment, applied twice daily, had a better
effect than tacrolimus ointment and placebo ointment once daily.”

2. On the other hand, subsequent studies report more encouraging
results. One published a year later did find topical tacrolimus as
effective as topical calcipotriol or betamethasone (each applied

Br J Dermatol 1999 Jul;141(1):103-7 
Tacrolimus ointment improves psoriasis in a microplaque assay.
Remitz A, Reitamo S, Erkko P, Granlund H, Lauerma AI.
Department of Dermatology, Helsinki University Central Hospital,
Meilahdentie 2, 00250 Helsinki, Finland.

“We describe the evaluation of two tacrolimus ointment formulations
for treatment of chronic plaque-type psoriasis. This was a microplaque
assay with randomized, double-blind design. Sixteen patients (15 men,
one woman, all white and 28-69 years old) with chronic plaque-type
psoriasis participated. Six different ointments were applied to
discrete microplaques, 17 mm in diameter, on a descaled psoriasis
lesion: these were tacrolimus ointment with diisopropyl adipate as
penetration enhancer, tacrolimus ointment without diisopropyl adipate,
0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol
ointment and, as controls, the ointment bases for tacrolimus and
betamethasone… Compared with the vehicle controls, sites treated with
tacrolimus ointment (with or without penetration enhancer) showed a
significant reduction in erythema and infiltration (P < 0. 001), a
significant reduction in superficial blood flow (P < 0.01) and a
significant decrease in epidermal thickness (P < or = 0.001). Results
for betamethasone and calcipotriol, when compared with the vehicle
controls, were similar. These results suggest that, under conditions
of descaling and occlusion, tacrolimus ointment is effective in the
treatment of psoriasis.”

3. A review published in 2000 stated that “Topical tacrolimus has not
been studied sufficiently in treating psoriasis although it has been
used successfully in allergic contact dermatitis, erosive mucosal
lichen planus and pyoderma gangrenosum” The author does say that
tacrolimus is 10-100 times more potent than cyclosporin A.
Clin Exp Dermatol 2000 May;25(3):250-4
Topical tacrolimus in dermatology.
Nasr IS.
Consultant Dermatologist, Scunthorpe General Hospital, Scunthorpe,
North Lincolnshire, UK.

4. Another review, also from 2000, states that: “Cyclosporine A (CyA),
well known from transplantation medicine for years, is licensed in
Germany for oral treatment of psoriasis and atopic dermatitis but is
not suitable for topical therapy. Tacrolimus (FK506) penetrates the
inflamed epidermis and is regarded as the key immunosuppressive
macrolide. Clinical trials have demonstrated the efficacy of FK506
ointment for atopic dermatitis, many case reports have been published
regarding other inflammatory skin diseases. The ascomycin derivative
ASM 981 has many of the properties of FK506 but less data is available
at present. Sirolimus (Rapamycin) is structurally related to FK506 but
has other biological effects since its molecular actions involve
different biochemical pathways.”
This review, in the German language, covers the “biochemical and
cellular properties, mode of action, therapeutic efficacy and unwanted
side effects, as well as data from clinical trials and status of
licensing”, so might be worth obtaining in full text, even though it
is slightly outdated.
Hautarzt 2000 Sep;51(9):646-54 
[Immunosuppressive macrolides and their use in dermatology]
[Article in German]
Bornhovd EC, Schuller E, Bieber T, Wollenberg A.
Klinik und Poliklinik fur Dermatologie und Allergologie,
Ludwig-Maximilians-Universitat Munchen.

5. A letter (no abstract available) reports the efficacy of topical
tacrolimus against facial psoriatic lesions in a clinical trial:
Acta Derm Venereol 2000 Nov-Dec;80(6):451 
Topical tacrolimus is effective for facial lesions of psoriasis.
Yamamoto T, Nishioka K.

6. Tacrolimus appears to be a better candidate than cyclosporin for
topical use.
Expert Opin Pharmacother. 2001 Jul;2(7):1167-75.
Topical tacrolimus for the treatment of inflammatory skin diseases.
Assmann T, Homey B, Ruzicka T.
Department of Dermatology, Heinrich Heine University, Duesseldorf,
“Cyclosporin, widely used in transplantation medicine, is also
effective in psoriasis and atopic eczema but is not suitable for
topical treatment. Tacrolimus (FK506) has been found to be 10-100
times more potent than cyclosporin and to penetrate skin much better
due to a lower molecular weight.” [The review appears to focus on
atopic eczema rather than psoriasis]

7. Nevertheless, last year, a group of authors still started their
abstract with the words, “Systemic but not topical tacrolimus (TAC) is
effective against psoriasis.”
Br J Dermatol 2002 Jun;146(6):964-7 
Liposomal tacrolimus lotion as a novel topical agent for treatment of
immune-mediated skin disorders: experimental studies in a murine
Erdogan M, Wright JR Jr, McAlister VC.
Department of Surgery, Dalhousie University, Halifax, Nova Scotia,

This study looked at ways to improve dermal absorption, but to have
this happen in a controlled manner, so as to minimise toxicity.
Liposomes were chosen as a delivery system.
“…topical application of LTAC achieved nine times the concentration of
TAC at a target site than did systemic administration of TAC….  LTAC
was more effective systemically than TAC in the prevention of
delayed-type hypersensitivity reactions. Topical LTAC also prevented
this response. CONCLUSIONS: Topical LTAC was effective in this model
of immune-mediated skin disease. Because LTAC achieves higher skin
concentrations than systemic TAC it may be an effective delivery
system for TAC in the treatment of psoriasis.”

8. However, a study this year declares topical tacrolimus to be
J Am Acad Dermatol. 2003 Apr;48(4):564-8. 
Tacrolimus ointment for the treatment of psoriasis on the face and
intertriginous areas.
Freeman AK, Linowski GJ, Brady C, Lind L, Vanveldhuisen P, Singer G,
Lebwohl M.
Mount Sinai School of Medicine, Department of Dermatology, New York,
NY 10029, USA.
“open-label, clinical trial of 21 patients with psoriasis. Patients
applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was
assessed through the investigator's evaluation of the individual signs
and symptoms of psoriasis, and the physician's global evaluation of
change in disease status…. A total of 81% of patients (17 of 21)
experienced complete clearance at day 57 (end of treatment). Only 2
patients reported adverse events, which were limited to itching and
the feeling of warmth at the application site. None of the patients
had atrophy, telangiectasia, or striae develop during the study. In
summary, tacrolimus 0.1% ointment may be a safe and effective
treatment option for patients with psoriasis on the face,
intertriginous areas, or both.”

9. A review of topical tacrolimus refers to mixed success in studies
of its use in psoriasis
“Although oral administration of tacrolimus proved to be efficacious
in psoriasis, results with topical tacrolimus have been disappointing
in some studies.”
Drugs Today (Barc). 2002 Jan;38(1):7-15. 
Topical tacrolimus Protopic.
Lazarous MC, Kerdel FA.
Department of Dermatology and Cutaneous Medicine, University of Miami
School of Medicine, Miami, FL 33136, USA.

10. The first mention of a macrolide topical therapy, which appeared
in 1996, refers not to tacrolimus but to another macrolide ascomycin
dervative, SDZ 281-240, which has a similar immunosuppressive
mechanism to tacrolimus, but does not show in vitro antiproliferative
activity against keratinocytes:
J Invest Dermatol 1996 Apr;106(4):701-10 
Clearing of psoriasis by a novel immunosuppressive macrolide.
Rappersberger K, Meingassner JG, Fialla R, Fodinger D, Sterniczky B,
Rauch S, Putz E, Stutz A, Wolff K.
Department of Dermatology, University of Vienna, Austria.
“…Our research therefore focuses on therapeutic strategies that induce
local immunosuppression in the skin by topical, transepidermal
delivery of immunosuppressive drugs...  To evaluate whether SDZ
281-240 exhibits antipsoriatic activity when applied topically, we
tested 15 patients with severe, recalcitrant psoriasis, using a
microplaque assay in randomized, double-blind, placebo-controlled
study…  All patients showed a significant improvement of psoriatic
lesions treated with two concentrations of the macrolide and, as
expected, with the corticosteroid but not with placebo. Both
concentrations of the macrolide led to clearing of psoriasis after 10
days of treatment and biopsies confirmed a reversal of the
histopathological and immunopathological phenotype of psoriasis to
that of normal skin… “

11. Another tacrolimus derivative or analogue, SDZ ASM 981
(pimecrolimus), has been found effective when applied topically under
Br J Dermatol 1998 Dec;139(6):992-6
The novel ascomycin derivative SDZ ASM 981 is effective for psoriasis
when used topically under occlusion.
Mrowietz U, Graeber M, Brautigam M, Thurston M, Wagenaar A, Weidinger
G, Christophers E.
Department of Dermatology, University of Kiel, Germany.
“Ten patients with chronic plaque-type psoriasis were treated with SDZ
ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and
open-labelled clobetasol-17-propionate ointment (0.05%) in a
randomized, double-blind, within-subject comparison for 2 weeks using
the microplaque assay… after 2 weeks of treatment, total scores
described [??? I think they mean decreased!] by 92% for clobetasol, by
82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the
ointment base (placebo). No adverse drug effects were seen in any
patient throughout the study. We conclude from our results that the
new macrolactam SDZ ASM 981 (1%) is similar to
clobetasol-17-propionate (0.05%) in plaque-type psoriasis… “

12.  European Journal of Dermatology. Vol. 9, Issue 5, June - August
1999: 346-51
Macrolide immunosuppressants
A review by Ulrich MROWIETZ, Department of Dermatology, University of
Kiel, Schittenhelmstr.
 7, 24105 Kiel, Germany.
“The mechanism of action of tacrolimus is similar to that of the first
immunosuppressant of fungal origin, cyclosporin A [2]. Both
cyclosporin A and tacrolimus are used worldwide for the prevention of
transplant rejection. In dermatology, cyclosporin A was shown to be
highly effective in the treatment of severe psoriasis and atopic
dermatitis as well as in a number of other indications such as
pyoderma gangrenosum and generalised lichen planus.
A major disadvantage in the clinical use of cyclosporin A for the
treatment of dermatological disorders is its lack of topical
effectiveness [3]. With the exception of the ulcerative phase of
pyoderma gangrenosum and erosive lichen planus of the mucosa, topical
treatment with cyclosporin A fails to improve dermatoses such as
psoriasis and atopic dermatitis where the systemic delivery is highly
effective [4, 5].”
This review is available in full text at
The references it gives to the lack of topical efficacy of cyckosporin
3. Mrowietz U. The enigma of cyclosporin A treatment in psoriasis:
systemic efficacy versus topical non-responsiveness. Acta Derm
Venereol (Stockh) 1992; 72: 321-6.
4. Theissen U, Luger TA, Schwarz T. Erfolgreiche topische Anwendung
von Cyclosporin A bei Pyoderma gangraenosum. Hautarzt 1996; 47: 132-5.
5. Eisen D, Ellis CN, Duell EA, Griffiths CEM, Voorhees JJ. Effect of
topical cyclosporin rinse on oral lichen planus. N Engl J Med 1990;
323: 290-4.

13. Nevertheless, an oral formulaton of cyclosporin dissolved in oil
did give encouraging results when used topically on psoriatic nails
Dermatology. 2003;206(2):153-6. 
Treatment of psoriatic nails with topical cyclosporin: a prospective,
randomized placebo-controlled study.
Cannavo SP, Guarneri F, Vaccaro M, Borgia F, Guarneri B.
Institute of Dermatology, University of Messina, Italy.
“ixteen adult patients with nail psoriasis, divided randomly into two
groups of 8 patients (group A and group B), were treated respectively
with a 70% maize-oil-dissolved oral CsA solution and maize oil alone….
 In group A, 3 patients came to a complete resolution of nail lesions
and 5 showed a substantial improvement of the overall severity score.
In group B, a slight improvement was noted in only 1 patient. All the
patients of group A judged positively the results of the therapy,
while in group B only 1 patient reported a moderate improvement.”

14. Electroporation increased the dermal penetration of cyclosporin,
but most of it remained bound to skin tissue
J Control Release. 1998 Jan 2;50(1-3):61-70.
Transdermal delivery of cyclosporin-A using electroporation.
Wang S, Kara M, Krishnan TR.
School of Pharmacy, Memorial University of Newfoundland, St. John's,
“Use of multiple pulses (25 pulses, 10 ms each) at Uelectrode 200 V
resulted in a sixty-fold increase, compared to passive, in the
delivery of CSA to the skin. Transdermally delivered CSA was mostly
bound to the skin and only a small amount was seen to cross the full
skin into the receiver compartment.”

15  European Journal of Dermatology. Vol. 7, Issue 7, October -
November 1997: 492-6,
Intralesional cyclosporine versus dithranol in the treatment of
plaque-type psoriasis
 Vesna M. PETRONI´C-ROSI´C  Jelena M. MARINKOVI´C   Olivera B.
Department of Dermatology and Venereology, University of Belgrade 
School of Medicine, Belgrade, Serbia, Yugoslavia.
“Standard cyclosporine parenteral solution consisting of cyclosporine
in a polyoxyethylated castor oil-alcohol vehicle (SandimmuneŽ,
original concentration 50 mg/ml) was diluted 1 part with 2 parts of
normal saline solution. The final concentration of the diluted
cyclosporine solution for injection was 17 mg/ml…. Subjects received
intradermal injections of 0.5 ml/cm2 (maximum 2 ml) of the
cyclosporine solution three times weekly (Monday, Wednesday, Friday)
at one site. Dithranol in Lassar's paste was applied for 20 hours
daily on the other site, beginning with the lowest concentration
(0.5%) and gradually increasing the concentration (to a maximal 2.0%)
according to the individual tolerance of every patient…. Intralesional
cyclosporine, administered three times a week for up to 4 weeks proved
more efficacious than dithranol applied 20 hours daily.
Full text at

Topical calcipotriene and betamethasone are more effective when
combined than when used separately:

16. J Am Acad Dermatol. 2003 Jan;48(1):48-54. 
Early onset of action and efficacy of a combination of calcipotriene
and betamethasone dipropionate in the treatment of psoriasis.
Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ,
Kaufmann R, Rogers S, van de Kerkhof PC, Hanssen LI, Tegner E, Burg G,
Talbot D, Chu A.
Probity Medical Research, Waterloo, Ontario, Canada.
“…international, multicenter, prospective, randomized, double-blind,
parallel-group, 4-week study in patients with psoriasis vulgaris
amenable to topical treatment…. A combination product of calcipotriene
50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle
shows superior efficacy with a more rapid onset of action than the new
vehicle containing either constituent alone in the treatment of
psoriasis vulgaris.”

17. Dermatology. 2002;205(4):389-93. 
A new calcipotriol/betamethasone dipropionate formulation (Daivobet)
is an effective once-daily treatment for psoriasis vulgaris.
Kaufmann R, Bibby AJ, Bissonnette R, Cambazard F, Chu AC, Decroix J,
Douglas WS, Lowson D, Mascaro JM, Murphy GM, Stymne B.
Goethe-Universitat, Frankfurt, Germany.
“1,603 patients were randomised to one of the 4 double-blind
treatments used once daily for 4 weeks… calcipotriol/betamethasone
dipropionate combination ointment used once daily is well tolerated
and more effective than either active constituent used alone”

18 Acta Derm Venereol. 2002;82(2):131-5. 
A new calcipotriol/betamethasone formulation with rapid onset of
action was superior to monotherapy with betamethasone dipropionate or
calcipotriol in psoriasis vulgaris.
Douglas WS, Poulin Y, Decroix J, Ortonne JP, Mrowietz U, Gulliver W,
Krogstad AL, Larsen FG, Iglesias L, Buckley C, Bibby AJ.
Department of Dermatology, Monklands Hospital, Lanarkshire, Scotland,
“106 patients were randomized to twice daily double-blind treatment
with combination, betamethasone dipropionate or calcipotriol for 4
weeks. Patients then received twice daily calcipotriol, unblinded, for
a further 4 weeks…. Calcipotriol/betamethasone combination is more
effective and has a more rapid onset of action than either active
constituent used alone, and is well tolerated. It is safe to transfer
patients from combination to calcipotriol, with maintenance of
clinical effect.”

19 AAD: Topical Cyclosporin A Conjugate Agent Shows Modest Efficacy
for Plaque Psoriasis
By Alison Palkhivala
“A topically applied cyclosporine A conjugate is showing modest
efficacy in early trials in patients with plaque psoriasis. The agent,
called CGC1072, employs a novel hepta-arginine conjugate designed to
deliver therapeutic levels of cyclosporine to the skin in a topical
David F. Fiorentino, MD, PhD, and colleagues from the department of
dermatology, Stanford University School of Medicine, California,
United States, performed a side-by-side comparison of 0.4% CGC1072,
4.0% CGC1072 and vehicle alone in 24 patients with mild to moderate
plaque psoriasis. Results were presented in a poster March 22nd here
at the 61st Annual Meeting of the American Academy of Dermatology…. At
the end of the trial, there was a trend toward the 4.0% CGC1072
product providing more effective clearing of psoriatic plaques than
placebo… A multicentre trial examining a more potent formulation is
currently underway, Dr. Fiorentino said.
The study was funded by CellGate, Inc., manufacturers of CGC1072”

You might also be interested in this press release from the Novartis
web site. It describes the results of gene profiling with DNA
microarrays of patients in a trial of pimecrolimus (oral
administration).  There appears to be a characteristic pattern of gene
expression that is associated with a response to treatment and is seen
within 13 days. This could provide a useful set of efficacy parameters
for use in future clinical trials.

Search strategy: 
Medline searches on: psoriasis and each of the drug names.
Supplemental searches on Google and with the same search

As always please request clarification if you require additional
information to this answer.

Best wishes

Clarification of Answer by tehuti-ga on 06 Jun 2003 12:42 PDT
Hello Tom,

I've found a further reference to the arginine complex:
Rothbard, J.B., Garlington S., Lin Q., Kirschberg, T., Kreider, E.,
McGrane, P.L., Wender, P.A., Khavari, P.A., Conjugation of
oligo-arginine to cyclosporine A facilitates topical delivery and
inhibition of inflammation. Nature Medicine 2000 Nov.; 6(11):1253-7.

This is from a bibliography on the Cellgate Inc web site

Request for Answer Clarification by tom136-ga on 07 Jun 2003 04:44 PDT
Dear Tehuti: Thank you very much for the reference to the arginine complex.

Clarification of Answer by tehuti-ga on 07 Jun 2003 05:48 PDT
Glad to have been of use, Tom. Thank you for the kind words and tip. 
I'm putting this in the clarification field to clear the alert in my
in box.
Best wishes, tehuti
tom136-ga rated this answer:5 out of 5 stars and gave an additional tip of: $3.00
Dear Tehuti. This is exactly what I asked you. Thank you! Regards,

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