IR & SR Pharmacokinetics IR Dose mg IR t 1/2 abs hrs SR Dose mg SR t 1/2 abs hrs Dose Interval hrs Duration days t 1/2 elim hrs Vd liters f (0.0 - 1.0)

 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. First Tmax is the time for the first peak. First Peak is the maximum concentration arising from the first dose. Last Peak is the maximum concentration from the last dose, which may be the steady-state value. Last Trough is the minimum concentration from just before the last 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.  April 14, 2009.
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