Minox Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: When applied topically, minoxidil has been shown to stimulate hair growth in individuals with alopecia androgenetica. The onset of hair growth stimulation occurs approximately after 4 or more months of use and is variable among patients. Upon discontinuation of minoxidil, new hair growth stops and restoration of pre-treatment appearance is expected within 3-4 months. The exact mechanism of action of minoxidil in the treatment of alopecia androgenetica is not known. Topical application of minoxidil showed no systemic effects related to absorption of minoxidil, when tested in controlled clinical trials in both normotensive and untreated hypertensive patients. In the treatment of hypertension, orally administered minoxidil has a direct peripheral vasodilator effect that reduces elevated systolic and diastolic blood pressure decreasing peripheral vascular resistance. Reduction of peripheral arteriolar resistance and the associated fall in blood pressure trigger sympathetic, vagal inhibitory and renal homeostatic mechanisms, including an increase in renin secretion, that lead to increased cardiac rate and output and salt and water retention. Minoxidil does not interfere with vasomotor reflexes and therefore does not produce orthostatic hypotension. In experimental animals the drug does not enter the central nervous system in significant amounts. Minoxidil does not affect CNS function in man.
Pharmacokinetics: Following the topical application of minoxidil, it is poorly absorbed from normal intact skin, with an average of 1.4% (range 0.3 - 4.5%) of the total applied dose ultimately reaching the systemic circulation. Therefore a 1ml dose of minoxidil 5%, delivering 50mg minoxidil to the skin, would result in absorption of approximately 0.7mg minoxidil. The effects of concomitant dermal diseases on absorption are unknown. Serum minoxidil levels resulting from topical administration of minoxidil are governed by the drug's percutaneous absorption rate. Following the cessation of topical dosing minoxidil, approximately 95% of systemically absorbed minoxidil is eliminated within 4 days. The metabolic biotransformation of minoxidil absorbed following topical application of minoxidil has not been fully determined. Minoxidil is almost completely absorbed from the gastrointestinal tract following oral administration of minoxidil tablets. It is metabolized predominantly by conjugation with glucuronic acid at the N-oxide position in the pyrimidine ring but also by conversion to more polar products. Known metabolites exert much less pharmacologic effect than minoxidil itself. Minoxidil does not bind to plasma proteins and its renal clearance corresponds to the glomerular filtration rate. Minoxidil does not cross the blood brain barrier. Minoxidil and its metabolites are hemodialyzable and are excreted principally in the urine.