Risultati e discussione
4.3 Risultati farmacocinetic
4.3.2 Somministrazione orale
La somministrazione orale di luteolina, sempre alla dose di 10 mg/Kg, ha portato ad una rapida presenza del flavone nel circolo sistemico dell’animale, in particolare ad un primo picco a 15 minuti nell’ordine degli 0,24µg/ml.
Nella fase seguente a questo primo picco si osserva una transitoria flessione delle concentrazioni plasmatiche ed una successiva ricomparsa di un picco a 2 ore, nell’ordine dei 0,27µg/ml.
È da notare che, sebbene nei vari esperimenti sia presente un’enorme variabilità, che molto probabilmente riflette ampie differenze inter-individuali nell’assorbimento e/o nel metabolismo di primo passaggio, la presenza di questa “bifasicità” di andamento delle concentrazioni plasmatiche, dopo somministrazione orale, è riscontrabile anche in altri studi (Chen et al., 2012).
L’ AUC0 →∞ relativa alla somministrazione orale di luteolina è risultata essere circa di 60µg/ml/min.
Tale parametro consente di stimare una biodisponibilità orale del flavone pari al 40%, valore che non si discosta in modo
55 significativo da quanto osservato da altri autori, in studi analoghi sulla stessa specie (Chen et al, 2012).
Figura 4.4: curva concentrazione vs tempo della luteolina dopo somministrazione endovenosa 0 100 200 300 400 500 0 100 200 300 min n g /m l lu te o lin a
56 I parametri farmacocinetici ottenuti sia dalla somministrazione endovenosa che da quella orale, sono schematizzati nella seguente tabella: Parametro farmacocinetico Somministrazione endovenosa di lutolina (10 mg/kg) Somministrazione orale di luteolina (10mg/kg) AUC0 →∞ (ng/ml/min) 145231 60440 t ½ (h) 1,6 Vd (l/kg) 1,7 Cmax (ng/ml) 13369 (a 5 minuti) 274 Biodisponibilità 42%
Questa tesi di laurea rappresenta quindi un lavoro preliminare che comunque ha consentito di ottimizzare e quindi mettere a disposizione del laboratorio di farmacologia del Dipartimento di Farmacia dell’Università di Pisa, un utile modello sperimentale
per gli studi più avanzati di farmacocinetica di luteolina e, più in generale, di flavonoidi.
La presente sperimentazione è finalizzata allo sviluppo di formulazioni innovative, atte a migliorare la biodisponibilità del flavone, quali ad esempio i fitosomi.
57
Capitolo 5
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73
Ringraziamenti
Per la prima volta, da quando ho iniziato a scrivere la tesi, non ho il ‘panico da pagina bianca’, forse perché da molto tempo
aspettavo di poter ringraziare tutte quelle persone che sono state presenti durante questi anni.
Per prima cosa mi sembra doveroso ringraziare chi mi ha permesso di compiere quest’ultimo e fondamentale passo: il dott. Vincenzo Calderone, senza il quale, questa bella esperienza non sarebbe stata possibile.
La pazienza infinita della dott.ssa Lara Testai nel seguirmi costantemente, il supporto morale della dott.ssa Alma Martelli e l’ambiente ricco di complicità delle mie compagne di laboratorio hanno reso l’esperienza indimenticabile.
Un ringraziamento speciale va ad Alice che mi ha accompagnato durante i primi passi.
Come dimenticare il supporto tecnico del laboratorio di Tossicologia Forense ed in particolare del dott. Silvio Chericoni e del dott. Fabio Stefanelli: grazie per i mille insegnamenti.
74 Ed ora mi sembra doveroso ringraziare la mia famiglia: i miei genitori e Niccolò che, da buon fratello, mi ha sempre supportato e consigliato: non poteva capitarmi di meglio. Grazie per essere esattamente come siete e incoraggiarmi, cercando sempre il meglio per me.
Siamo giunti alla parte difficile: gli amici! Premetto che se non troverete il vostro nome non dovrete prendervela, siete tantissimi, fortunatamente,e vi ringrazio dal profondo del cuore per aver perso qualche minuto a leggere queste pagine.
Mi sembra giusto partire da colei che mi ha accompagnato per 20 anni di studio: tra alti e bassi siamo arrivate a questo traguardo, grazie Gianna.
Il mio Tess, basta uno sguardo, non servono parole..Feda,una sorella adottata, Cli, Na, Tata..anche se non ci vediamo spesso, bastano poche battute per ricreare il feeling che c’è sempre stato.
È doveroso ringraziare tutti gli amici che mi hanno accompagnato durante questi anni: Vale, Robe, Paola, Chiara, Marzia, Bea ed Elisa, senza di voi tutto sarebbe stato molto più difficile.
75 Grazie a Luca per la pazienza nel leggere tutta l’introduzione pur non sapendo assolutamente di cosa parlasse e a Giulia per le passeggiate rilassanti, il burraco, le serate a spettegolare..(sarà il caso che riscopriamo la nostra gioventù?! )
C’è chi mi ha sopportato e supportato fin dalla prima superiore
come Lele e chi è arrivata qualche anno dopo, ma ha subito recuperato, come Elisa.
Ed ultimo, ma non certamente per importanza, ringrazio il mio fidanzato, Nicolò, per esserci e per esserci stato, per avermi sopportato, per ogni sorriso che mi hai strappato e perchè ho sempre trovato un sostegno in te ..GRAZIE.