Dear March05,
Thank you for your question on finasteride. From RxList.com, there is
a good description of the pharmacokinetics of finasteride:
http://www.rxlist.com/cgi/generic3/propecia_cp.htm
From this reference, finasteride works primarily on the Type II
isozyme of the 5-alpha reductase. Here is a quote:
"In humans, the mechanism of action of finasteride is based on its
preferential inhibition of the Type II isozyme. Using native tissues
(scalp and prostate), in vitro binding studies examining the potential
of finasteride to inhibit either isozyme revealed a 100-fold
selectivity for the human Type II 5a-reductase over Type I isozyme
(IC50=500 and 4.2 nM for Type I and II, respectively). For both
isozymes, the inhibition by finasteride is accompanied by reduction of
the inhibitor to dihydrofinasteride and adduct formation with NADP+.
The turnover for the enzyme complex is slow ([half-life] approximately
30 days for the Type II enzyme complex and 14 days for the Type I
complex)."
This means, as one commentator stated, that the half-life of the
enzyme after long term exposure to finasteride is approximately 30
days.
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From the Drug Information Handbook (Authors: Lacy, Charles F.,
Armstrong, Lora L., Goldman, Morton P., Lance, Leonard L.), 12th
edition, here is more information on the pharmacokinetics of
finasteride:
"Onset of action: 3-6 months of ongoing therapy
Duration: After a single oral dose as small as 0.5 mg: 65% depression
of plasma dihydrotestosterone levels persists 5-7 days
After 6 months of treatment with 5 mg/day: Circulating
dihydrotestosterone levels are reduced to castrate levels without
significant effects on circulating testosterone; levels return to
normal within 14 days of discontinuation of treatment
Distribution: Vdss: 76 L
Protein binding: 90%
Metabolism: Hepatic via CYP3A4; two active metabolites (<20% activity
of finasteride)
Bioavailability: Mean: 63%
Half-life elimination, serum: Elderly: 8 hours; Adults: 6 hours (3-16)
Time to peak, serum: 2-6 hours
Excretion: Feces (57%) and urine (39%) as metabolites"
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From the US Pharmacopea, Information for the Health Care Professional,
there is additional information (and some corroboration of the above):
"Absorption:
Finasteride is rapidly absorbed from the gastrointestinal tract. Mean
bioavailability of a 5-mg tablet was 63% (range 34 to 108%) in a study
in healthy male subjects. Mean bioavailability of a 1-mg tablet was
65% (range 26 to 70%) in a study in healthy male subjects.
Bioavailability is not affected by food intake.
Distribution:
Finasteride crosses the blood-brain barrier. It also is distributed
into semen; however, the amount of finasteride in the semen of
patients receiving 5 mg per day has no effect on circulating DHT
concentrations in adults.
Volume of distribution (Vol D) ? Steady state: 76 L
Protein binding:
Plasma ? Very high (90%).
Biotransformation:
Hepatic. The major metabolite isolated from urine is the
monocarboxylic acid metabolite; the t-butyl side chain
monohydroxylated metabolite has been isolated from plasma. These
metabolites have no more than 20% of the 5-alpha-reductase inhibiting
activity of finasteride.
Half-life:
Mean 6 hours (range 3 to 16 hours) following a single 5-mg dose in
healthy male subjects 45 to 60 years of age; approximately 8 hours in
subjects 70 years of age or older. Mean 4.5 hours after multiple 1 mg
doses in males 19 to 42.
[Bear in mind that this is the half-life of the drug, not the enzyme.]
Time to peak concentration:
Plasma ? Ranged from 1.8 to 2.8 hours after administration of single
doses of 5, 10, 20, 50, and 100 mg of finasteride and 1 to 2 hours
after administration of multiple doses of 1 mg per day.
Peak serum concentration:
Plasma ? Ranged from 38.1 ± 7 to 835.5 ± 199.2 micrograms per L
(mcg/L) after administration of single doses of 5, 10, 20, 50, and 100
mg of finasteride and 9.2 nanograms per mL (range 4.9 to 13.7
nanograms per mL) after administration of multiple doses of 1 mg per
day. Slow accumulation occurs with multiple dosing; in one study, mean
plasma concentrations were approximately 50% higher after 17 days of
treatment than after the first dose, and mean trough concentrations in
another study after 1 year were even higher. In one study, the mean
area under the plasma concentration - time curve (AUC) (0 to 24 hours)
after 17 days of administration was 15% higher in subjects 70 years of
age or older.
Time to peak effect
Reduction in serum DHT concentration ? 8 hours after the first dose.
Duration of action:
Single dose ? Reduction in serum DHT concentration: 24 hours.
Multiple doses ? DHT concentrations return to pretreatment levels
within approximately 2 weeks after withdrawal of daily therapy. The
prostate returns to pretreatment size in about 3 months.
Elimination:
Fecal, 57% (range 51 to 64%), as metabolites; renal, 39% (range 32 to
46%), as metabolites. In renal function impairment, urinary excretion
of metabolites is decreased, but fecal excretion of metabolites is
increased; therefore, no dosage adjustment is necessary.
In dialysis ? Unknown. "
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I hope this information was useful. Please feel free to request clarification.
-welte-ga |
