Multidose Pharmacokinetics Loading Dose mg Repeating Dose mg Dose Interval hrs Duration days t 1/2 abs hrs t 1/2 elim hrs Vd liters f (0.0 - 1.0)

 This page allows viewing of a multidose pharmacokinetics profile. To use enter the following parameters: Loading Dose: Start with a loading dose of zero. A suggested loading dose will be given in the results text field. The value of the Loading Dose is added to the Repeating Dose for the value of the total first dose. Repeating Dose: This is the dose given at each interval, including the first dose. If you want to examine a single dose, set the Loading Dose to zero, keep this as the single dose and set the Dose Interval to a ridiculously large number. 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 abs: This is the absorption half-life. For an immediate release dosage form, an absorption half-life is usually about 0.5 to 1.0 hours. For sustained release dosage forms, the absorption half-life may be about 2 to 3 hours. The absorption rate, ka, is related to the half-life by ka = ln(2)/(t 1/2 abs). To mimic an intravenous bolus dose, set the t 1/2 abs to a very small number, say 0.001 hr. To mimic continuous infusion, set the t 1/2 abs to a very low number and set the Dose Interval to a similarly small number. 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. This does not include the Loading Dose, just the amount in the Repeating Dose. Cp Max is the peak value of the blood level. Cp Min is the trough value of the blood level, which occurs just prior to the second dose. If you make the Dose Interval a ridiculously big number, then the Cp Min will become zero. t Max is the timepoint at which Cp Max occurs. AUC is the area under the curve of the blood levels for the repeating dose going out to infinite time. The next part gives the long-term steady-state values. Cp Max is the peak value of the blood level. Cp Avg is the average value of the blood level. Cp Min is the trough value of the blood level, which occurs just prior to the following dose. t Max is the timepoint at which Cp Max occurs after a dose. Note that this is not the same as the t max for a single dose. AUC is the area under the curve of the blood levels for the dose interval. Note that since this is calculated at steady state, the value is the same as the AUC for a single dose going out to infinite time. The Suggested Loading Dose is that amount which when added to the Repeating Dose brings the initial peak up to the steady state level. Again, the Loading Dose in this calculation is the amount added to the Repeating Dose for the initial 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's an example comparing a multidose pharmacokinetics profile with and without a loading dose. Other pages by Jeffrey Clymer. Email.
Debut: April 2, 2009.  Revision No. 1.  April 2, 2009.
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