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 ATTIVO
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
 Dosaggio
 Peso Molecolare dei FANS
 % assorbimento del
principio attivo
 Grado di Lipofilia
 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 applicationExclusive 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/cm2)
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
High elasticity
Perfect 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 20mg 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 20mg 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 20mg 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, 1plaster/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, 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
CONCLUSIONI
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