INTRODUCTION
The pathogenesis of acne vulgaris depends upon several key
factors including keratinization abnormalities, excess sebaceous
gland secretion, the presence and activity of the anaerobic
bacterium Propionibacterium acnes (P. acnes), and
inflammatory immune reactivity.1 Clinical experience has
shown that simultaneously targeting one or more of the pathogenic
factors using a combination of appropriate drugs is the
most effective approach to treating acne vulgaris. Combinations
of antibiotics (clindamycin phosphate and erythromycin)
with antimicrobial agents (benzoyl peroxide) and topical
retinoids have all been shown to improve acne.2-22
Treatment with a combination of a topical retinoid plus an antimicrobial
agent is a logical therapeutic approach based upon
their different, and additive, mechanisms of action, including
suppression of toll-like receptor 2 (TLR-2) activation by topical
retinoids.23-25 The combination targets 3 pathogenic factors:
abnormal follicular keratinization, proliferation of P. acnes,
and inflammation.2-19 This produces a faster and greater resolution
of lesions (comedones and inflammatory lesions) compared
to monotherapy, improves antimicrobial penetration,
and reduces the risk of low concentration-induced antibiotic
resistance.2-4
Clindamycin phosphate 1.2% and tretinoin 0.025% gel
(CLIN/RA Gel [Zianaâ„¢]) is the newest topical combination
agent approved by the US FDA for the treatment of acne vulgaris
in patients 12 years of age or older. This product uses innovative
technology to combine an antimicrobial, clindamycin
phosphate (1.2%), and a topical retinoid, tretinoin (0.025%),
in a single formulation that is applied once per day.26
Clindamycin Phosphate 1.2% and Tretinoin 0.025% (CLIN/RA Gel)
Description and Mechanism of Action
In this novel product a solution of clindamycin phosphate
1.2% (equivalent to 1% clindamycin) and a suspension of
crystalline tretinoin 0.025% are combined in a patented alcohol-
free, aqueous-based gel vehicle. In solution, tretinoin
is unstable in an aqueous environment; however, this product
uses tretinoin in its solid rather than liquid form.
Tretinoin is refined to a microcrystalline powder and placed
in suspension within the aqueous based gel. Because the solubility
of tretinoin in water is low the tretinoin crystals remain
in a stable solid form until dissolved on the skin.
Results from a 6-week, phase I dermal safety and sensitization
(occlusive patch test) study in 229 healthy subjects highlighted
the value of the novel delivery system and vehicle.
That study evaluated the cumulative irritation potential and
contact sensitization potential of CLIN/RA gel and the
CLIN/RA gel vehicle compared to tretinoin 0.025% gel
(Retin-A gel), which contains the same amount of tretinoin
solubilized in an alcoholic base. Investigators concluded that
both the CLIN/RA gel and the CLIN/RA vehicle had a very
low potential for causing sensitization reactions and significant
irritation. CLIN/RA gel was significantly less irritating
than tretinoin gel 0.025% (P<.001). The results showed
that a formulation of tretinoin in a crystalline suspension
without alcohol makes a significant difference in irritation.27
Certainly the suspension of crystalline tretinoin in the vehicle
gel improves the stability of tretinoin, and it may also
provide a means of slow or delayed release of tretinoin into
the skin. While the exact mechanism is under investigation,
the clinical efficacy and effects suggest that tretinoin dissolves
slowly and produces a steady delivery of tretinoin over time.
This slow release may ensure that the concentration of
tretinoin in the skin does not overwhelm retinoid receptors,
