Hello all, I have a questions regarding calculation of volume of distribution and clearance for single dose of Amphotericin B injection. Study design is open label, randomized, two-treatment, two period, two-sequence, single dose, crossover, comparative pharmacokinetic study in healthy adult human subjects under fed conditions. Dose mode of administration is single dose of Amphotericin B liposome for injection (3 mg/kg body weight). Dose was given to subjects with respective subject weight i.e. Suppose subject No.01, weight 73 and dose 3mg/kg then total dose= 73 kg * 3 mg/kg =219 mg. I had calculated administration VD and CL based on the non-compartmental model using IV infusion dose type. Following information’s was provided in dosing sheet in winNonlin software.

Sub-1, period-1, dose-219mg, time of dose-0, Length of Infusion-2 sub-1, period-2, dose-219mg, time of dose-0, Length of Infusion-2.01 PK parameter calculations VD and CL values obtained from winNonlin were not matching with reference article WinNonlin results of VD and CL is as below Sub VD (mL) CL (mL/hr) 1 29759.19 833.3955 1 821.759 sub-1, period-1, VD (mL)-29759.19, CL (mL/hr)-833.3955 sub-1, period-2, VD (mL)-82120.74, CL (mL/hr)-1029.759 Could anyone please guide me how to estimate VD and CL in mL/kg and mL/hr/kg in winNonlin software. Is there any option available to find out VD and CL in mL/kg and mL/hr/kg.

Thanks in advance Edit: Unlinked from, category changed. Hi Kumar, I don’t have spare time to check the setup. One question first: Which version of WinNonlin? » PK parameter calculations VD and CL values obtained from winNonlin were not matching with reference article Can you give us these values? Remarks: • I have no experiences with this liposomal product, but I guess you don’t assume F=1 (otherwise why did you perform such a study?). If this is the case, infusion is not the correct NCA-model – use an extravasal model instead. Then you’ll get Vd/F and CL/F, where 0.

The population mean and SD (including imprecision) of the NPDEs are compared with the expected values (i.e. Mean 0, SD 1) in forest plots. The probability density of the NPDE values for the entire population is produced and compared with respect to the normal distribution with mean 0 and variance 1. Individual level diagnostics2.2.2.1. The mean PK parameters for ABX464 after a single oral administration of 50–200 mg are reported in Table 3 and mean ABX464 plasma concentration–time profiles are shown in Figure 1. C max was observed between 1.75 and 2 h after dosing (ranging from 0.66 to 4 h) in all groups with mean values ranging from 14 to 72 ng/mL.

Dear Helmut, Thanks for the response. I have used winNonlin 6.3 version for PK calculations.

(Reference article values of Vd and CL) The pharmacokinetic parameters of total amphotericin B (mean ± SD) after the first dose and at steady state are shown in the table below. I used dosing information in winNonlin i.e., 219 000 ug instead of 219 mg. In the NCA- setup select Norma­li­zation and kg is worked, I found unit correctly but still Cl and Vd values were not matches with reference article. After dose conversions I got same results WinNonlin result of Vd and Cl is as below: Subject Period VZ (mL/kg) CL(ml/hr/Kg) 1 1 29759.19 833.39545 1 2 821.7594 Reference: Prescribing information of AmBisome® (amphotericin B) liposome for injection from Astellas Pharma US, Inc.

[cited 18 December, 2013]. Dear Kumar, Can you not post the whole PHXPROJ and then we can see easily how you have set things up? The table on page 4 of the paper you reference is mean data at 3 dose levels on day 1 and last day, but you've give what appear to be two individual results without it being clear to me at what dose level/status.

What is your objective? I only briefly skimmed the paper but it's clear that they had problems estimating a 'true' half-life and also that there was some considerable variability. Nfs server and file permissions ntfs. Get tips and discuss Pharsight products with other users. Hello Simon, Study was carried out with following objective To compare the rate and extent of absorption of amphotericin B after intravenous administration of single dose of Amphotericin B liposome for injection (each vial containing amphotericin 50 mg encapsulated in liposomes) with that of AmBisome® liposome for injection (each vial containing amphotericin 50 mg encapsulated in liposomes) in healthy adult human subjects in a randomized crossover study under fed conditions.