Chemical formula: C₉H₁₅N₅O Molecular mass: 209.248 g/mol PubChem compound: 4201
Topical administration of minoxidil stimulates hair growth in men and women with androgenic alopecia. The mechanism of stimulating hair growth from minoxidil is not fully understood, but some actions of minoxidil include increasing hair diameter, stimulating new growth and prolonging the developmental phase, and stimulating hair follicle transition from resting phase (telogen) in the growth phase (regenerative).
Minoxidil stimulates hair growth in persons with early and moderate stages of hereditary hair loss (alopecia androgenetica). This hair loss appears in women with a reduction in hair density (thinning) and widening of the part line on the central part of the scalp, which may include a breach of the frontal hairline (female pattern hair loss).
Minoxidil can reverse the hair loss process of androgenetic alopecia by the following means:
As a peripheral vasodilator minoxidil enhances microcirculation to hair follicles. The Vascular Endothelial Growth Factor (VEGF) is stimulated by minoxidil and VEGF is presumably responsible for the increased capillary fenestration, indicative of a high metabolic activity, observed during the anagen phase.
The systemic absorption of topically applied minoxidil from normal intact skin is low.Systemic absorption of minoxidil from topically applied solution ranges between 1% and 2% of the total applied dose compared to 90-100% of the oral formulation.
The systemic absorption of minoxidil from a 5% foam formulation has been estimated in a 2-arm pharmacokinetic study in subjects with androgenetic alopecia, which included twice-daily 5% topical solution or 2% topical solution as comparators.
The systemic absorption of minoxidil from twice daily application of 5% minoxidil foam was about half of that observed with 5% minoxidil solution. The mean steady state AUC(0-12 hr) and Cmax for 5% minoxidil foam, 8.81 ng·hr/mL and 1.11 ng/mL, respectively, were both approximately 50% of AUC(0-12 hr) and Cmax of the 5% solution, 18.71 ng·hr/mL and 2.13 ng/mL, respectively.
The AUC of 5% minoxidil foam used once daily was found to be similar to that of 2% minoxidil solution used twice daily in female subjects.
The time to maximum minoxidil concentration (Tmax) for the 5% foam, 5.42 hr, was similar to Tmax for the 5% solution, 5.79 hr. The haemodynamic effects of minoxidil do not become evident until mean serum minoxidil concentrations reach 21.7 ng/mL.
There is some evidence from in vitro studies that minoxidil reversibly binds to human plasma proteins. However, since only 1–2% of topically applied minoxidil is absorbed, the extent of plasma protein binding occurring in vivo after topical application would be clinically insignificant. The volume of distribution of minoxidil doses between 1.37 mg and 27.4 mg at steady state after 12-hour intravenous administration ranges from 76.0 to 82.8, respectively.
Approximately 60% minoxidil absorbed after topical application is metabolised to minoxidil glucuronide, primarily in the liver.
The half-life of topical minoxidil averaged 22 hours, compared to 1.49 hours for the oral formulation. Minoxidil and its metabolites are excreted almost entirely in the urine (97%), with a very minor degree of elimination via the faeces (3%).
Renal clearance of minoxidil and minoxidil glucuronide calculated from oral data averaged 261 mL/min and 290 mL/min, respectively.
Following cessation of dosing, approximately 95% of topically applied minoxidil will be eliminated within four days.
Preclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential.
Cardiac effects of minoxidil in dogs are species-specific in terms of low doses that cause profound haemodynamic effects and associated changes in the heart. Available data indicate that similar cardiac effects do not occur in humans treated topically or orally with minoxidil.
Minoxidil showed no evidence of mutagenic/genotoxic potential in a number of in vitro and in vivo assays.
A high incidence of hormone-mediated tumours was observed in mice and rats. These tumours are due to the secondary hormonal (hyperprolactinemia) effects observed only in the rodents at extremely high doses by a mechanism similar to that seem with reserpine. Application of topical minoxidil has not demonstrated any effect on hormonal status in women. Therefore, hormonally mediated tumour promotion by minoxidil does not represent a carcinogenic risk to humans.
Animal reproduction toxicity studies in rats and rabbits have shown signs of maternal toxicity and a risk to the foetus at exposure levels that are very high compared to those, intended for human exposure. There is a risk of foetal harm in humans.
Preclinical fertility studies in rats have shown minoxidil doses equal or greater than 3 mg/kg/day (at least 8 fold human exposure) when administered orally and greater than 9 mg/kg (at least 25-fold human exposure) administered subcutaneously in rats were associated with reduced conception and implantation rates as well as reduction in the number of live pups.
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