INTRODUCTION
Doxycycline 40 mg modified-release capsules (30 mg
immediate-release and 10 mg delayed-release beads),
administered at a daily dosage of one capsule daily, is
the first and only oral medication approved by the US Food and
Drug Administration (FDA) for the treatment of papulopustular (PP)
rosacea, also referred to as subtype 2 rosacea. This formulation
has been specifically referred to as anti-inflammatory dose
doxycycline in the peer-reviewed medical literature, including
in the pivotal phase III study publication, as its pharmacokinetic
(PK) and microbiologic profiles demonstrate absence of antibiotic
selection pressure with a lack of emergence of antibiotic-resistant
bacterial strains.1-4 Specifically, this modified-release oral 40 mg
capsule formulation administered once daily differs in PK profile
from immediate-release doxycycline tablets, capsules, and liquids,
and from other delayed-release oral formulations of doxycycline,
such as enteric-coated pellets embedded in a tablet or capsule
hull. Importantly, this specific doxycycline 40 mg capsule allows
for immediate release of 30 mg of doxycycline, followed later
during intestinal transit by release of 10 mg of doxycycline from
delayed-release beads, providing a PK profile that is unique and not bioequivalent to other doxycycline products.1 In addition, the plasma concentrations of doxycycline achieved with oral intake of
this modified-release doxycycline 40 mg capsule once daily are
in the range which provides anti-inflammatory effects unrelated
to antibiotic activity, and are below those required to achieve
minimum inhibitory concentrations needed to suppress bacteria.1-4
Thus, this specific modified-release doxycycline 40 mg capsule
formulation (30 mg immediate release and 10 mg delayed release
beads) coupled with once daily administration, hereafter referred to
as anti-inflammatory dose doxycycline, was intentionally designed
to achieve anti-inflammatory effects while at the same time avoiding
the antibiotic effects that occur with other doxycycline formulations
dosed at equal to or greater than 50 mg daily.2-5 Another advantage of
anti-inflammatory dose doxycycline demonstrated in a randomized,
double-blind, active-control, comparative 16-week study is the
nearly identical speed of onset and magnitude of effectiveness in
patients with predominantly moderate PP rosacea based on lesion
count reductions and investigator's global assessment (IGA), but
with a five-fold lower incidence of gastrointestinal adverse events
as compared to doxycycline 100 mg once daily.5
