Dermatology

Acquired expertise in healthy volunteers and/or patients

1. Basic PK studies: The release of a test drug from a topical formulation, its percutaneous absorption, systemic bioavailability and safety are determined in HV and patients administered by single/multiple doses of gels, creams, ointments, foams, plasters, patches, films, etc. The relationships existing between the measured kinetic parameters and the site of application, the skin properties, the environmental conditions, and the patch adhesiveness, can be investigated (1-2).

2. Safety studies: With the aim of assessing the local tolerability & sensitisation potential, dermal irritation, photo-toxicity and photo-sensitisation are performed following protocols as for the relevant guidelines (4).

3. Topical corticosteroids (Cs): Topical Cs exerts vasoconstriction on the peripheral dermal vessels causing skin blanching. The magnitude of this effect is measured using colorimetric techniques and it is accepted as a surrogate variable BA when a Cs-product is applied to the skin. It is then possible to establish the BE between 2 topical products containing the same quali-quantitative composition in Cs and excipients.

4. Percutaneous absorption: In vivo PK data on the penetration into sub-epidermal layers of a test drug is possible by employing microdialysis and 2-D ultrasound. The technique is based on diffusion of analytes from the extra-cellular space through a semi-permeable membrane. The process is accomplished in vivo by a probe perfused with a physiological solution at low flow rate. Once probe is implanted into the tissue, substances diffuse from the extra-cellular fluid into the perfusion medium, which is collected and analysed (3).

5. Skin Biopsy: Androgenetic alopecia depends both on genetic predisposition and on the local presence of androgen dihydrotestosterone (DHT) which is formed from testosterone (T) by a 5-alpha reductase. Patients with androgen insensitivity syndrome and type-2 5-alpha reductase deficiency, show activation of follicular androgen receptors by DHT. In males undergoing a pharmacological treatment with a test drug T and DHT concentrations can be concurrently analysed in scalp biopsies and serum (5-6).

6. Efficacy trials: Study protocols designed to investigate the efficacy of a test drug in patient populations with different dermatological pathologies (acne, alopecia, herpes, psoriasis, atopic dermatitis) have been developed by Cross and can be tailored for other test molecules.

References

(1) Brunner M, Davies D, Martin W, Leuratti C, Lackner E, Müller M. "A new topical formulation enhances relative diclofenac bioavailability in healthy male subjects." Br J Clin Pharmacol. 2011 Jan 17. PubMed

(2) Monti D, Herranz U, Dal Bo L, Subissi A. "Nail penetration and predicted mycological efficacy of an innovative hydrosoluble ciclopirox nail lacquer vs. a standard amorolfine lacquer in healthy subjects." J Eur Acad Dermatol Venereol. 2013 Feb. PubMed

(3) Burian A, Frangione V, Rovati S, Mautone G, Leuratti C, Vaccani A, Crevenna R, Keilani M, Burian B, Brunner M, Zeitlinger M. "An exploratory microdialysis study investigating the effect of repeated application of a diclofenac epolamine medicated plaster on prostaglandin concentrations in skeletal muscle after standardized physical exercise." Br J Clin Pharmacol. 2013 Apr 1. PubMed

(4) Di Stefano A F D, Radicioni M M, Vele A, Mancarella Eberhardt A, Caccia G, Focanti F, Salvatori E, “Tolerability and hydrating effects of an anti-aging gynaecological collagen cream in women in menopause” OJOG. 2014 Feb; Vol.4, No.3. OJOG

(5) Caserini M, Radicioni M, Leuratti C, Annoni O, Palmieri R, "A novel finasteride 0.25% topical solution for androgenetic alopecia: pharmacokinetics and effects on plasma androgen levels in healthy male volunteers." Int J Clin Pharmacol Ther. 2014 Oct; 52(10):842-9. PubMed

(6) Caserini M, Radicioni M, Leuratti C, Terragni E, Iorizzo M, Palmieri R, “Effect of a novel finasteride 0.25% topical solution on scalp and serum dihydrotestosterone in healthy men with androgenetic alopecia”. International Journal of Clinical Pharmacology and Therapeutics. 2016; 54:19-27. PubMed

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