Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties
Pharmacotherapeutic group: other dermatologicals, ATC code: D11AX 
Individual responses to minoxidil 2% are variable and unpredictable.

The effect of minoxidil 2% has been assessed in phase III clinical trials in women conducted over a 48 week treatment period.

In these studies minoxidil 2% was compared to the product vehicle without the minoxidil active ingredient. The primary efficacy criterion was non-vellus hair count in a 1.0 cm2 reference area of affected scalp.
The mean changes observed in this parameter in these studies were significantly in favour of minoxidil 2% and were as follows:


Mean change in non-vellus hair count in reference 1 cm2 area of scalp compared with baseline minoxidil 2%                    Vehicle                Pairwise comparison
Baseline              150.4                       138.4
Mean change from            Mean change from baseline                    baseline
16 weeks              +35.9                       +20.0                  2%>vehicle 32 weeks              +26.7                       +15.2                  2%>vehicle 48 weeks              +20.7                        +9.4                  2%>vehicle

Using non-vellus hair count as an efficacy criteria, minoxidil 2% has also been shown to stabilise hair loss (defined as re- growth or no loss) in 88% of patients compared with 69% of patients who received vehicle in one trial following 48 weeks treatment and in 87% of patients compared with 73% of patients who received vehicle in a further trial following 32 weeks treatment.

Female patients’ own evaluations in clinical studies have shown that hair growth was reported by approximately 60% of females after 8 months of minoxidil 2% usage.

Patient evaluation of visible hair growth
% of Females                % of Females reporting regrowth          reporting regrowth after 8 months              after 4 months minoxidil 2% usage          Product vehicle usage
Minimal re-growth                          30-40                       29-33 Moderate to dense re-growth                20-25                        7-12 Total                                      55-59                       40-41 
In addition, minoxidil 2% has been shown to stabilise hair loss (shown as re-growth or no loss) in 4 out of 5 females as calculated from two clinical studies that showed stabilisation with 88 and 87% respectively while corresponding figures for vehicle were 69 and 74%.
The mechanism by which minoxidil stimulates hair growth is not fully understood, but minoxidil can reverse the hair loss process of androgenetic alopecia by the following means:
- increase the diameter of the hair shaft
- stimulate anagen growth
- prolong the anagen phase
- stimulate anagen recovery from the telogen phase

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.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
The failure to detect evidence of systemic effects during treatment with minoxidil solution reflects the poor absorption of topically applied minoxidil from normal intact skin. Systemic absorption of minoxidil from topically applied solution ranges between 1% and 2% of the total applied dose.

In a study in males, the minoxidil serum concentration time curve (AUC) for the 2% solution averaged 7.54 ng·h/ml compared to a mean AUC of 35.1 ng·h/ml for the 2.5 mg oral formulation. The mean peak plasma concentration (Cmax) for the topical solution was 1.25 ng/ml, compared to18.5 ng/ml following the 2.5 mg oral dose.

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 after intravenous administration has been estimated at 70 litres.

Approximately 60% minoxidil absorbed after topical application is metabolised to minoxidil glucuronide, primarily in the liver. Minoxidil and its metabolites are excreted almost entirely in the urine, with a very minor degree of elimination via the faeces. Following cessation of dosing, approximately 95% of topically applied minoxidil will be eliminated within four days.