Farmaci topici 

Marco PaoloniMarco Paoloni

XX CONGRESSO NAZIONALE SICD - ROME REHABILITATION 2011Sindromi algiche del distretto lombo-sacrale e dell’arto inferiore

Site of inflammation: Site of inflammation:

Not always inflamed sites can be easily reached by drugs through systemic circulation

Passaggio di sostanze dalla superficie esterna della cute agli strati sottostanti

TERAPIA TRANSDERMICATERAPIA TRANSDERMICA

Preparati per uso topicoPreparati per uso topico

PRINCIPIO ATTIVO VEICOLO

ATTIVITA’ FARMACOLOGICA (PROMOTORI DI

ASSORBIMENTO)

ECCIPIENTI

Preparati per uso topicoPreparati per uso topico

UNGUENTIUNGUENTI

PASTEPASTE

POMATE/CREMEPOMATE/CREME

SCHIUME MEDICATESCHIUME MEDICATE

GELGEL

CEROTTI MEDICATICEROTTI MEDICATI

La via transdermicaLa via transdermica

Elettiva localizzazione nel sito di infiammazioneElettiva localizzazione nel sito di infiammazione

Assenza degli effetti collateralisistemici tipici dei FANS per via oraleAssenza degli effetti collateralisistemici tipici dei FANS per via orale

Azione più rapida sul sito di infiammazioneAzione più rapida sul sito di infiammazione

Il successo della via transdermicaIl successo della via transdermica

CARATTERISTICHE DEL PRINCIPIO ATTIVO

Dosaggio Peso Molecolare dei

FANS % assorbimento del principio attivo Grado di Lipofilia Sede infiammata da

raggiungere

Tecnologiadel sistema transdermico

Caratteristiche di ketoprofeneCaratteristiche di ketoprofene

Indometacina

PM 350 dalton

Piroxicam

PM 330 dalton

Diclofenac

PM 325 dalton

Ketoprofene

PM 260 dalton

Flurbiprofene

PM 250 dalton

KETOPROFENE ha un basso Peso Molecolare KETOPROFENE ha un basso Peso Molecolare

0

100

100

- +-

+

Efficacy

Perc

uta

neou

s a

bsorb

an

ce

wit

hin

4 h

ou

rs (

%)

KP

DC

FP

IM

KP = ketoprofeneFP = flurbiprofeneDC = diclofenacIM = indometacine

Absorbance/Efficacy of ketoprofene is higher

than other NSAIDs

Particularly suitable for transdermic application

(Yano et al.)

% of absorbance of the active principle% of absorbance of the active principle

Relazione tra lipofilia e assorbimento cutaneoRelazione tra lipofilia e assorbimento cutaneo

1 2 3 4 5

2

1

Logari

tmo d

ella

% d

i ass

orb

imento

AU

MEN

TO

AS

SO

RB

IMEN

TO

Logaritmo del coefficiente di ripartizione(n-ottanolo/acqua)

AUMENTO LIPOFILIA

Diclofenac

Indometacina

Ketoprofene

Flurbiprofene

KETOPROFENE ha un valore di log p= 2,94 prossimo al valore ottimale ed è quindi uno dei FANS con la più alta permeabilità percutanea

KETOPROFENE ha un valore di log p= 2,94 prossimo al valore ottimale ed è quindi uno dei FANS con la più alta permeabilità percutanea (Tadanori et al.)

Valore ottimale

TECNOLOGY OF THE TECNOLOGY OF THE

TRANSDERMIC SYSTEMTRANSDERMIC SYSTEM

MOLECULE TRANSDERMIC SYSTEM

Diclofenac Natural rubber based

Flurbiprofene Natural rubber based

Ketoprofen Non aqueous matrix (SIS system = Styrene -Isoprene- Styrene)

Non aqueous matrix topical plaster application - SIS

ketoprofen 20 mg Topical plaster applicationketoprofen 20 mg Topical plaster application

KetoprofenKetoprofen

BaseBase

Sustained release of the active Sustained release of the active principleprinciple

technology

ketoprofen 20 mg Topic plaster application- ketoprofen 20 mg Topic plaster application- Exclusive matrix polimeric SISExclusive matrix polimeric SIS

3 component copolymer:- Styrene-Isoprene- Styrene

Includes and structures the ketoprofen in a stable

and regular way

Even and steady release of the active principle

continuously

Ideal structural propertiesIdeal structural properties

The SIS matrix guides the Ketoprofen release

Improving its percutaneous permeability

Ketoprofen

ONCE A DAY APPLICATION Sustained release within 24 hours

Kuzumaki N et al

ketoprofen 20 mg topical plaster application– ketoprofen 20 mg topical plaster application– Exclusive polymeric matrix SISExclusive polymeric matrix SIS

ketoprofen 20 mg Topical plaster application:ketoprofen 20 mg Topical plaster application:Absorption and action speedAbsorption and action speed

Quanti

ty o

f p

rod

uct

ab

sorb

ed

by s

kin

aft

er

a s

ing

le a

pp

licati

on (g

/cm

2)

Hours

Takada Y et al

Quantity of active principle detected in the skin after a single topic application of Quantity of active principle detected in the skin after a single topic application of Ketoprofen, Flubiprofene o DiclofenacKetoprofen, Flubiprofene o Diclofenac

High elasticity Perfect adhesion

Suitable also in flexible areas

ketoprofene 20 mg topic plaster: Advantagesketoprofene 20 mg topic plaster: Advantages

Optimal Adhesion and flexibilityOptimal Adhesion and flexibility

Intra-articular absorption and distribution of Ketoprofen after topical plaster application and oral intake in 100 patient undergoing knee arthroscopy Reumatology 1999; 38: 564-567 Rolf C. et al

Objective: Assessment of the kinetic of ketoprofen in synovial fluid and intra-articular tissue in relation to plasma.

Methods: Ketoprofen concentration was analyzed in plasma, synovial fluid and intra-articular tissues after single application of 30 mg plaster or oral intake of 50 mg in patients undergoing knee arthroscopy.

Results : median Cmax values after topical application were 12.8 ng/ml in synovial fluid, 56.7 ng/g in synovial tissue, 349.3 ng/g in meniscus and 568.9 ng/g in cartilage.

Conclusion: topical application of ketoprofen allow the attainment of high intra-articluar tissue concentration.

Tissue Median Cmax T

Median Cmax O

Synovial tissue

Meniscus

Cartilage

Plasma

Synovial fluid

56,7

349,3

568,9

18,7

12,8

363,9

85,7

83,5

2595,3

353,8

Reumatology 1999; 38: 564-567 Rolf C. et al

Intra-articular absorption and distribution of Ketoprofen after topical plaster application and oral intake in 100 patient undergoing knee arthroscopy

Symptomatic treatment of Pain and inflammation caused by Acute Osteo muscular diseases

such as trauma, strains and bruisings

ketoprofen 20 mg Topic plaster application:ketoprofen 20 mg Topic plaster application:Indication :Indication :

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic affect

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic affect

Percent of patients showing an improving of the back pain, patients without benefits and declined despite the previous condition after 2 weeks therapy, with oral ketoprofen 50 mg t.i.d. (n. 62) or topic transdermic ketoprofen plaster(n.59).

Comparison with oral ketoprofen in the low back pain

Sugioka Y et al

Double blind trial involving 184 patients comparing Ketoprofen topic plaster (1 plaster/day ) and oral ketoprofen 50 mg 3 times/day, for 2 weeks.

General improving of signs and symptoms of low back pain

% o

f p

atie

nts

Takagishi N et al

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic effect

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic effect

Trial utilizing ketoprofen plaster, 1plaster/day for 2 weeks involving 174

patients suffering different post-traumatic diseases

Improving of 63% in Scapulo Humeralis Periartritis

70% of patients improve in the other diseases

Aoki T e et al

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic affect

Ketoprofen 20mg topic plaster application:

anti-inflammatory and antalgic affect

Dalla Letteratura…

Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD007402. DOI: 10.1002/14651858.CD007402.pub2

CONCLUSIONICONCLUSIONI

La terapia con FANS topici si dimostra efficace e sicura nel

trattamento delle condizioni muscoloscheletriche acute

La scelta dell’uso del trattamento per via topica è dettata da

fattori legati al tipo di lesione ed al tipo di molecola