Hi, I am currently working on a non-compartmental analysis (NCA) of a study involving iron sucrose (injectable solution, 100 mg/5 mL), administered as an intravenous bolus injection over 5 minutes. In this context, time zero is defined as the moment immediately after the end of the drug administration.
The sampling times used in the study are as follows (in hours): -0.58; -0.25; 0.00; 0.08; 0.17; 0.25; 0.50; 1.00; 2.00; 4.00; 5.00; 6.00; 8.00; 10.00; 12.00; 24.00; 36.00
I have attached an image showing the configuration I am considering for the NCA object. I would greatly appreciate your guidance on whether this setup is appropriate for this type of administration and sampling design.
- Model Type: Plasma (200-202)
- Dose Options: IVBolus
- Calculation Method: Lineal Up Log Down
- Unit: mg
- Dosing: Time =0; Dose (mg) = 100
Best regards,
VNYazigi
Dear Nicolas,
Within Phoenix, the time 0 should be at the start of the dose time, negative times will be ignored, please review this section of the help.
I personally would be tempted to set this as a 5 min infusion, since you appear to have samples taken whilst the bolus was administered.
Simon, thank you very much for your quick response.
Following up on your comments, I would like to share my understanding and confirm whether the following configurations are appropriate for the NCA analysis in this case:
SCENARIO 1: IVBolus
I have reviewed the help section regarding “Data Checking and Pre-treatment” rules. To confirm my interpretation, here is the scenario:
- Administration Type:** IV Bolus
- Sampling times (hours): -0.58; -0.25; 0.08; 0.17; 0.25; 0.5; 1; 2; 4; 5; 6; 8; 10; 12; 24; 36. Note: Time zero corresponds to the end of drug administration (no sample was collected at t = 0).
- Example dataset:
|Sample | Time (h) | Concentration (ug/dL)|
|V1-1 | -0.58 | 0 |
|V1-2 | -0.25 | 0 |
|V1-3 | 0.08 | 349 |
|V1-4 | 0.17 | 195 |
|V1-5 | 0.25 | 210 |
|V1-6 | 0.50 | 136 |
|V1-7 | 1 | 132 |
|V1-8 | 2 | 84 |
|V1-9 | 4 | 66 |
|V1-10 | 5 | 60 |
|V1-11 | 6 | 100 |
|V1-12 | 8 | 47 |
|V1-13 | 10 | 57 |
|V1-14 | 12 | 25 |
|V1-15 | 24 | 0 |
|V1-16 | 36 | 0 |
QUESTION 1: Is this understanding correct?: In an NCA analysis with IV Bolus administration, Phoenix will attempt to back-extrapolate C₀ using a log-linear regression between the first two valid points (with time ≥ 0), meaning that the pre-dose samples (-0.58 h and -0.25 h) will be ignored** when estimating C₀.
QUESTION 2: Given that the administration type is IV Bolus and time zero corresponds to the end of the administration (with no sample at t = 0), I would like to confirm whether the following settings are appropriate:
- Model Type: Plasma (200-202)
- Dose Options: IV Bolus
- Calculation Method: Linear Up Log Down (based on the guidance in this article)
- Unit: mg
- Dosing: Time = 0; Dose = 100 mg
SCENARIO 2: Short Infusion
Additionally, I understand the suggestion to consider this case as a 5-minute infusion, since it appears that samples were collected during the administration of the bolus. If I were to take that approach, and based on the same dataset, would the following configuration be correct?
- Administration Type: IV Infusion
- Sampling times (h): Same as listed above
- Model Type: Plasma (200-202)
- Dose Options: IV Infusion
- Calculation Method: Linear Up Log Down
- Unit:mg
- Dosing: Time = 0; Dose = 100 mg; Infusion Length = 0.08333 hours (5 minutes)
Thank you in advance for your guidance.
Kind regards,
Nicolás
Nicolas, I would first recommend you re-calculate your time to relative to start of dose i.e. add 5mins to all times using a Data Wizard. THen I the assumptions it makes will be better, otherwise I think you settings look OK for either route of administration
Multiple people have mentioned samples being taken during administration, but according to OP’s definition of time zero as end of administration, I can see no sampling occurring during administration. There was a -15 minute sample, and with a 5 min infusion, this would have occurred 10 min prior to the start of administration. There was also a 5 minute time point post-end-of-infusion. The OP specifies there were no samples collected at t=0 when defined as end of infusion. I would also recommend using setting up the NCA as a 5 minute infusion as opposed to a bolus but following other posters’ suggestion to define t=0 as start of infusion. I believe OP’s Scenario 2: Short Infusion setup would be correct. Sampling time points would need to be adjusted to be relative to start of infusion as others have mentioned.
