Farmaci topici Marco Paoloni XX CONGRESSO NAZIONALE SICD

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

Site of inflammation: Not always inflamed sites can be easily reached by drugs through systemic circulation

TERAPIA TRANSDERMICA Passaggio di sostanze dalla superficie esterna della cute agli strati sottostanti

Preparati per uso topico PRINCIPIO ATTIVITA’ FARMACOLOGICA VEICOLO ECCIPIENTI (PROMOTORI DI ASSORBIMENTO)

Preparati per uso topico UNGUENTI PASTE POMATE/CREME GEL SCHIUME MEDICATE CEROTTI MEDICATI

La via transdermica Elettiva localizzazione nel sito di infiammazione Assenza degli effetti collaterali sistemici tipici dei FANS per via orale Azione più rapida sul sito di infiammazione

Il successo della via transdermica CARATTERISTICHE DEL PRINCIPIO ATTIVO Ø Dosaggio Ø Peso Molecolare dei FANS Ø % assorbimento del principio attivo Ø Grado di Lipofilia Ø Sede infiammata da raggiungere Tecnologia del sistema transdermico

Caratteristiche di ketoprofene Indometacina Diclofenac PM 350 dalton PM 325 dalton Ketoprofene Piroxicam PM 260 dalton PM 330 dalton Flurbiprofene PM 250 dalton KETOPROFENE ha un basso Peso Molecolare

% of absorbance of the active principle Percutaneous absorbance within 4 hours (%) + - 100 KP FP DC KP = ketoprofene FP = flurbiprofene DC = diclofenac IM = indometacine IM 0 - Absorbance/Efficacy of ketoprofene is higher than other NSAIDs 100 Efficacy + (Yano et al. ) Particularly suitable for transdermic application

Logaritmo della % di assorbimento AUMENTO ASSORBIMENTO Relazione tra lipofilia e assorbimento cutaneo 2 Ketoprofene Flurbiprofene Valore ottimale Indometacina Diclofenac 1 1 2 3 4 Logaritmo del coefficiente di ripartizione (n-ottanolo/acqua) 5 AUMENTO LIPOFILIA 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. )

TECNOLOGY OF THE TRANSDERMIC SYSTEM MOLECULE TRANSDERMIC SYSTEM Diclofenac Natural rubber based Flurbiprofene Natural rubber based Ketoprofen Non aqueous matrix (SIS system = Styrene Isoprene- Styrene)

ketoprofen 20 mg Topical plaster application Non aqueous matrix topical plaster application - SIS technology Sustained release of the active principle Base Ketoprofen

ketoprofen 20 mg Topic plaster application. Exclusive matrix polimeric SIS Ideal structural properties 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

The SIS matrix guides the Ketoprofen release Improving its percutaneous permeability

ketoprofen 20 mg topical plaster application– Exclusive polymeric matrix SIS Sustained release within 24 hours ONCE A DAY APPLICATION Ketoprofen Kuzumaki N et al

Quantity of product absorbed by skin after a single application (mg/cm 2) ketoprofen 20 mg Topical plaster application: Absorption and action speed Hours Quantity of active principle detected in the skin after a single topic application of Ketoprofen, Flubiprofene o Diclofenac Takada Y et al

ketoprofene 20 mg topic plaster: Advantages Optimal Adhesion and flexibility üHigh elasticity üPerfect adhesion Suitable also in flexible areas

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 intraarticular 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 56, 7 363, 9 Meniscus 349, 3 85, 7 Cartilage 568, 9 83, 5 Plasma 18, 7 2595, 3 Synovial fluid 12, 8 353, 8

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

ketoprofen 20 mg Topic plaster application: Indication : Symptomatic treatment of Pain and inflammation caused by Acute Osteo muscular diseases such as trauma, strains and bruisings

Ketoprofen 20 mg topic plaster application: anti-inflammatory and antalgic affect Comparison with oral ketoprofen in the low back pain 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). Sugioka Y et al

Ketoprofen 20 mg topic plaster application: anti-inflammatory and antalgic effect % of patients General improving of signs and symptoms of low back pain Double blind trial involving 184 patients comparing Ketoprofen topic plaster (1 plaster/day ) and oral ketoprofen 50 mg 3 times/day, for 2 weeks. Takagishi N et al

Ketoprofen 20 mg topic plaster application: anti-inflammatory and antalgic affect Improving of 63% in Scapulo Humeralis Periartritis 70% of patients improve in the other diseases Trial utilizing ketoprofen plaster, 1 plaster/day for 2 weeks involving 174 patients suffering different post-traumatic diseases Aoki T e et al

Dalla Letteratura…

Massey T, Derry S, Moore RA, Mc. Quay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No. : CD 007402. DOI: 10. 1002/14651858. CD 007402. pub 2

CONCLUSIONI q. La terapia con FANS topici si dimostra efficace e sicura nel trattamento delle condizioni muscoloscheletriche acute q. La scelta dell’uso del trattamento per via topica è dettata da fattori legati al tipo di lesione ed al tipo di molecola