A single centre, open‐label, cross‐over study of pharmacokinetics comparing topical zinc/clindamycin gel (Zindaclin®) and topical clindamycin lotion (Dalacin® T) in subjects with mild to moderate acne

Abstract

Zinc/clindamycin gel (Zindaclin 1%) gel, is a new once-daily topical acne treatment (Strakan Ltd) containing clindamycin phosphate equivalent to 1% clindamycin and zinc acetate in a formulation, which leads to a reduced systemic absorption of clindamycin through the skin. The objective of the study was to compare the systemic absorption of clindamycin from zinc/clindamycin gel and clindamycin lotion (Dalacin T topical lotion, Pharmacia Ltd) after repeated twice-daily topical administration for two periods of 5 days with an intervening gap of 2 weeks in 24 subjects with mild to moderate acne. Plasma Cmax, and AUC0-12 of clindamycin measured after single and multiple applications of zinc/clindamycin gel were between 30% and 50% lower than for clindamycin lotion. As zinc/clindamycin gel is a topical treatment for acne, the lower systemic bioavailability may be beneficial because there may be a correspondingly lower risk of systemic events in zinc/clindamycin gel-treated subjects.

Topical clindamycin in the management of acne vulgaris

“…In a 5-day crossover study of clindamycin 1% lotion and zinc/clindamycin 1% gel, median clindamycin peak plasma concentrations were reduced by 41% on day 1 and 34% on day 5, and areas under the plasma concentration-time curve were reduced by 49% on day 1 and 36% on day 5 with the zinc-containing formulation (all p < 0.05). Similar findings were noted with trough plasma concentration and urinary excretion data [46] . Topical clindamycin does not alter the systemic bioavailability of concurrent tretinoin [42] .…”

Clindamycin phosphate scavenges hydroxyl radical

“…This study clearly reveals that CLDMP has a potent capacity to scavenge hydroxyl radical directly, but not superoxide anion. Although the generation of reactive oxygen species (ROS) through myeloperoxidase and NADPH oxidase (NADPH, reduced nicotinamide adenine dinucleotide phosphate) by phagocytic cells, such as neutrophils, is known to be an important host defense mechanism directed towards the killing of invading microorganisms, 17,18 ROS have potential deleterious effects on the biological system, as they can damage proteins, lipids, and nucleic acids 5–7 . In the case of NADPH oxidase, superoxide anions are generated, and the dismutation of superoxide anion then generates hydrogen peroxide, which gives rise to hydroxyl radical formation through a Fenton‐type reaction 19–22 .…”

“…It is available as CLDM hydrochloride for oral administration in capsules, as CLDM phosphate (CLDMP) for intramuscular or intravenous injection, and as CLDM palmitate for oral suspension 3 . In addition to intramuscular or intravenous injection, CLDMP is the most widely used topical antibacterial agent for acne treatment because of its proven safety and efficacy in many clinical studies 4–7 . Recently, it has been reported that CLDM has anti‐inflammatory properties, such that it reduces tumor necrosis factor‐α (TNF‐α) concentration in lipopolysaccharide (LPS)‐stimulated THP‐1 cells, and decreases serum TNF‐α and interleukin‐1β (IL‐1β) concentrations and increases serum IL‐6 concentrations in the mouse model 8,9 .…”

The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

“…That which can be provided by stable isotope studies includes: Data demonstrating the maximal plasma/serum zinc concentration obtained relative to dose (which relates to optimal absorption of zinc using zinc stable isotope kinetics), duration of effect and timing of the doses. These data can be provided using zinc stable isotope techniques [ 158 , 159 , 160 , 161 ]. Delivery of zinc to the target tissue as informed by the volume of distribution, by plasma protein binding and, if needed, tissue biopsy assays.…”

“…Data demonstrating the maximal plasma/serum zinc concentration obtained relative to dose (which relates to optimal absorption of zinc using zinc stable isotope kinetics), duration of effect and timing of the doses. These data can be provided using zinc stable isotope techniques [ 158 , 159 , 160 , 161 ].…”