CLINICAL PHARMACOLOGY
In humans, the natural supply of vitamin D depends mainly
on exposure to the ultraviolet rays of the sun for conversion
of 7-dehydrocholesterol to vitamin D3 (cholecalciferol)
in the skin. Calcipotriene is a synthetic analog of vitamin
D.
Clinical studies with radiolabeled ointment indicate
that approximately 6% (*3%, SD) of the applied dose of
calcipotriene is absorbed systemically when the ointment
is applied topically to psoriasis plaques or 5% (*2.6%,
SO) when applied to normal skin, and much of the absorbed
active is converted to inactive metabolites within 24
hours of application.
Vitamin D and its metabolites are transported in the
blood, bound to specific plasma proteins. The active form
of the vitamin, 1,25- dihydroxy vitamin D3 (calcitriol),
is known to be recycled via the liver and excreted in
the bile. Calcipotriene metabolism following systemic
uptake is rapid, and occurs via a similar pathway to the
natural hormone. The primary metabolites are much less
potent than the parent compound.
There is evidence that maternal 1,25-dihydroxy vitamin
D, (calcitriol) may enter the fetal circulation, but it
is not known whether it is excreted in human milk. The
systemic disposition of calcipotriene is expected to be
similar to that of the naturally occurring vitamin.
CLINICAL STUDIES
Adequate and well-controlled trials of patients treated
with DOVONEX have demonstrated improvement usually beginning
after two weeks of therapy. This improvement continued
in patients using Dovonex once daily and twice daily.
After 8 weeks of once daily Dovonex, 56.7% of patients
showed at least marked improvement (6.4% showed complete
clearing). After 8 weeks of twice daily Dovonex, 70.0%
of patients showed at least marked improvement (11.3%
showed complete clearing).
Subtracting percentages of patients using placebo (vehicle
only) from percentages of patients using Dovonex who had
at least marked improvement after 8 weeks yields 39.9%
for once daily and 49.6% for twice daily. This adjustment
for placebo effect indicates that what might appear to
be differences between once and twice daily use may reflect
differences in the studies independent from the frequency
of dosing. Although there was a numerical difference in
comparison across studies, twice daily dosing has not
been shown to be superior in efficacy to once daily dosing.
Over 400 patients have been treated in open label clinical
studies of DOVONEX for periods of up to one year. In half
of these studies, patients who previously had not responded
well to DOVONEX were excluded. The adverse events in these
extended studies included skin irritation in approximately
25% of patients and worsening of psoriasis in approximately
10% of patients. In one of these open label studies, half
of the patients no longer required DOVONEX by 16 weeks of
treatment because of satisfactory therapeutic results.
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