Sanbe-Hair Mechanism of Action

Pharmacology: Pharmacodynamics: When applied topically, Minoxidil topical solution has been shown to stimulate hair growth in individuals with androgenetic alopecia (male pattern baldness). Although the exact mechanism of action of Minoxidil in the treatment of androgenetic alopecia is not known, there may be more than one mechanism by which Minoxidil stimulates hair growth. They include: (a) vasodilation of the microcirculation around the hair follicles which may stimulate hair growth; (b) direct stimulation of the hair follicle cells to enter into a proliferative phase: resting phase (telogen) follicles being stimulated to pass into active phase (anagen) follicles; (c) alteration of the effect of androgens on genetically predetermined hair follicles: Minoxidil may affect the androgen metabolism in the scalp by inhibiting capacity of androgens to affect the hair follicles.
Finasteride is a type II 5-α-reductase inhibitor, an intracellular enzyme that converts androgen testosterone to 5-α-dihydrotestosterone (DHT). Inhibition of 5-α-reductase inhibitors will block the conversion of testosterone to DHT, thereby reducing the concentration of DHT in serum and tissue.
In men with male pattern hair loss (androgenetic alopecia), the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Application of Finasteride decreases scalp DHT concentration in these man, which may contribute to the treatment effect of Finasteride. By this mechanism, Finasteride appears to interrupt a key factor in the development of androgenetic alopecia in those patients who are genetically predisposed.
Pharmacokinetics: Following topical application of Minoxidil topical solution, Minoxidil is poorly absorbed from normal intact skin, with an average of 1.4% (range 0.3% to 4.5%) of the total applied dose reaching the systemic circulation. The effects of concomitant dermal diseases or occlusion on absorption are unknown. Serum Minoxidil levels resulting from topical administration are governed by the drug's percutaneous absorption rate; increases in surface area of application do not result in proportionate increases in the serum Minoxidil level. Steady state is achieved by the end of the third dosing interval (36 hours) when the drug is administered twice daily. Approximately 95% of the systematically absorbed Minoxidil from topical dosing is eliminated within 4 days. The metabolic biotransformation of Minoxidil absorbed following topical application has not been fully determined.
Known metabolites exert much less pharmacologic effect than Minoxidil itself, and all are excreted principally in the urine. Minoxidil does not bind to plasma proteins; its renal clearance corresponds to glomerular filtration rate and it does not cross the blood brain barrier. Minoxidil and its metabolites are hemodialyzable, although this does not rapidly reverse its pharmacological effect.
Increased hair growth has not been associated with increased systemic absorption of topical Minoxidil. The onset of hair growth stimulation requires twice daily applications of Minoxidil topical solution for 4 or more months and is variable among patients. Upon discontinuation of topically applied Minoxidil, new hair growth has been subjectively reported to stop and restoration of pretreatment appearance to occur within 3 to 4 months.
The pharmacokinetics of Finasteride following topical administration has not been evaluated systematically. However, it is expected that it will be poorly absorbed from normal intact skin, with a minimal of the total applied dose reaching the systemic circulation.