Toledo — Benzoyl peroxide has been used for acne since the 1960s in various over-the-counter and prescription creams, lotions and washes. It remains the most cost-effective acne regimen by some accounts (Lancet 2004;364:2188).
It may be possible to make a more effective benzoyl peroxide product via a stimulant, an accelerator and modification of the vehicle.
Our basic premise is that the most active biological form of benzoyl peroxide is its radical state. This is certainly true in chemistry and in industry. For example, benzoyl peroxide radicals initiate a process called polymerization that is for used for human bone cements and for mending cracks on the wings of airplanes. Benzoyl peroxide radicals have also demonstrated increased antibacterial coverage.
Accepting this tenet, the preferred stimulant for the formation of radicals is a tertiary amine, which is a substance that has an accessible nitrogen molecule that is already partially saturated with carbon molecules. This tertiary amine readily converts benzoyl peroxide into its more active radical state by the transference of electrons.
Erythromycin and clindamycin have tertiary amines in their chemical structures. It would be our contention that the expanded antibacterial coverage and clinical benefit of combining these two antibiotics with benzoyl peroxide is in the higher production of benzoyl peroxide radicals (and not the mere fact that both agents have antibacterial properties). My son, who is now a dermatology resident at Chapel Hill, revealed the synergistic activity of benzoyl peroxide and erythromycin, explained the biochemistry of this reaction, and offered a method to quantitate benzoyl peroxide radicals in Skin Pharmacology and Skin Physiology (2000;13:292-296). Additionally, we have performed studies seemingly revealing that one can achieve equal results (to the combination of benzoyl peroxide with erythromycin and/or clindamycin) using other tertiary amines, which are not antibiotics, with benzoyl peroxide.
From chemistry and industry, we know that trace metals, such as zinc, can accelerate this reaction (between benzoyl peroxide and a tertiary amine) by reducing the energy level needed for the production of benzoyl peroxide radicals.
There are several methods by which one can alter the environment to maximize the production of benzoyl peroxide radicals. One method is simply warming the skin with light or heat. The reaction is also more productive when the base has low water content with a lot of PEG units.
Benzoyl peroxide radicals are formed and have their biological effects within seconds. It is our belief that one should mix the benzoyl peroxide with the tertiary amine on the skin surface to maximize clinical results.
In the coming year we should have two publications on our in vivo and in vitro findings on combining benzoyl peroxide with tertiary amines so that others can properly assess the value of our research.
Dr. Burkhart is clinical professor at the Medical University of Ohio at Toledo.