This page allows viewing of a multidose pharmacokinetics
profile from immediate-release (IR) and sustained-release
(SR) drugs.
To use enter the following parameters: IR Dose: This is
the
amount of the immediate-release portion of the dose. For a
sustained-release product this is normally no more than
half the total
dose. IR t 1/2 abs: This is the absorption half-life for the immediate-release portion of the dose, usually about 0.5 to 1.0 hours. The absorption rate, ka, is related to the half-life by ka = ln(2)/(t 1/2 abs). SR Dose: This
is the amount of the sustained-release portion of the
dose. This is
generally more than half the total dose. t 1/2 abs: This is the absorption half-life for the sustained-release portion of the dose, usually about 2 to 3 hours. The absorption rate, ka, is related to the half-life by ka = ln(2)/(t 1/2 abs). Dose Interval:
This is
the
time interval between doses. Generally a
dose interval is chosen to be approximately equal to the
elimination
half-life.
If you want to see what a single, non-repeating dose looks
like, set
the Dose Interval to a ridiculously large number, say
10,000 hours. Duration: This is
the
duration of the pharmacokinetics profile that
will be displayed. t 1/2 elim: This
is
the
elimination half-life. The elimination rate, ke, is
related to the
half-life by ke = ln(2)/(t 1/2 elim). Because of a quirk
in the
mathematics, don't set the absorption and elimination
half-lives equal
to each other. When determining ke and ka from blood data,
something
horrible called flip-flop kinetics occurs if ke is greater
than ka. But
that horribleness does not carry over to this calculation,
so relax. Vd: This is the
volume
of
distribution. You only need to know this if you want exact
values for
blood levels. f: This is the
fraction of
drug absorbed or the bioavailability. You only need to
know this if you
want exact values for blood levels. After you hit the Replot! button, the PK profile is
replotted
and
the text of the data is inserted into the text box. The
text starts off
with a rehash of the input data and includes calculation
of ka, ke and
clearance. The Clearance
is
calculated as the product of ke and Vd. The text then provides values resulting from the first
dose. Lastly, the time (t)
and
blood level (Cp)
data are
given. These data may be copied and pasted into an Excel
or Google
spreadsheet for better control over graphing, or for
displaying
multiple curves on the same graph. Here are two examples comparing multidose
pharmacokinetics
profiles. In the first example, a 4-hour IR dose with an
0.75-hr
absorption half-life is compared to an 8-hour SR dose with
a 2-hr
absorption half-life. For both the elimination half-life
is 4 hrs. In the second example, three curves have been generated
in
which the dosage is either all IR, all SR or an even split
between the
two. The parameters are the same as the first example,
except that all
dosing is done in an 8-hour interval. |
Other pages
by Jeffrey Clymer. Email.
Debut: April 14, 2009. Revision No. 1.
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