Fifty Years of Minocycline and Its Evolution: A Dermatological Perspective

October 2021 | Volume 20 | Issue 10 | Original Article | 1031 | Copyright © October 2021


Published online September 24, 2021

Hilary E. Baldwin MD FAADa, Daniel B. Ward, Jr. MD FAADb

aThe Acne Treatment and Research Center, Brooklyn NY and Rutgers Robert Wood Johnson Medical Center, Newark, NJ
bDermoEpidermal Junction Consulting, Charleston, SC

Abstract
2021 is the 50th anniversary of the FDA approval of minocycline (MCN). While many other antibiotics have become obsolete during this time, MCN continues to be quite useful. In dermatology, MCN is used prominently in acne vulgaris, and is also employed in many other dermatological conditions because of its molecular and pharmacological properties. In this article, we review the history of minocycline, and outline the evolution of the drug since its inception. Based on its existing longstanding utility and continued innovations in formulation and delivery systems, we postulate that it will continue to have a prominent position in the dermatologist’s armamentarium.

J Drugs Dermatol. 2021;20(10):1031-1036. doi:10.36849/JDD.6370

INTRODUCTION

This year, 2021, is the 50th anniversary since the 1971 FDA approval of minocycline (MCN) and its introduction into the dermatologist’s toolbox. Over those same 50 years, multiple antibiotics have proceeded from auspicious launch to functional obsolescence,1 while MCN continues to be an integral dermatological therapeutic. Its inherent favorable molecular characteristics and pharmacokinetics have been complemented by an evolution of incremental improvements in dosing, formulation, and delivery systems that have led to its ongoing, longstanding utility. Whereas it was originally approved for systemic infections such as pneumonia and those of the genitourinary tract,2 in dermatology MCN has been employed for a whole host of cutaneous conditions ranging from rosacea to confluent and reticulated papillomatosis,3 central centrifugal cicatricial alopecia,4 pyoderma gangrenosum,5 methicillin-resistant Staphylococcus aureus,6,7 and many others. Most notably however, its lipophilicity as well as anti-microbial and anti-inflammatory properties has made it particularly suitable for the predominant therapeutic use in dermatology, acne vulgaris.

The Tetracycline Class of Antibiotics
Tetracycline (TCN) itself was discovered in the 1940’s, and FDA-approved in 1953. Although effective in the treatment of acne, TCN required frequent (QID) dosing, and had a prominent side effect profile, including common gastrointestinal (GI) disturbances, and photosensitivity. Also, it was vulnerable to antibiotic resistance, and therefore is no longer a standard treatment option. The TCN derivatives: doxycycline (1967), minocycline (1971), and sarecycline (2018), were chemically adapted (primarily via modifications on carbons 7–9 on the D ring) to reduce side effects and provide additional therapeutic benefits.8-10

These derivatives share common mechanisms of action in the treatment of acne. They are transported into bacterial cells where they bind to the 30S unit of the ribosome, and subsequently inhibit protein synthesis, thereby suppressing the proliferation of Cutibacterium acnes. A Gram-positive anaerobic rod, C. acnes, is the primary bacterium in acne vulgaris.11-14 In addition to its antibacterial action, the TCN class also exhibits a variety of anti-inflammatory properties. It has been shown to suppress neutrophil chemotaxis, inhibit pro-inflammatory cytokines such as TNF-α and IL-1β, reduce C. acnes lipase enzymes, decrease matrix metalloproteinases, and reduce arachidonic acid metabolites.15,16 These anti-inflammatory actions may be particularly important considering increasing evidence that acne is primarily an inflammatory disorder with inflammation preceding the development of clinically recognizable lesions.17,18

Together, the TCN class makes up approximately three-quarters of all antibiotics prescribed in dermatology.19 The class is considered first-line for acne except where it is contraindicated,20 whereas the macrolides and trimethoprim sulfamethoxazole are secondary alternatives.20,21 Hydrophilic antibiotics such as penicillin and the cephalosporins are thought to be less effective because a lack of lipophilicity prevents adequate distribution into the pilosebaceous unit,22 although there is limited evidence showing some efficacy.23

Although oral antibiotics are highly effective in the treatment of acne, concerns regarding their overuse contributing to the global incidence of antibiotic resistance are valid. Responsible