Population pharmacokinetic modelling of NS2330 (tesofensine) and its major metabolite in patients with Alzheimer's disease.

Lehr T, Staab A, Tillmann C, Trommeshauser D, Raschig A, Schaefer HG, Kloft C

British journal of clinical pharmacology23 Feb 2007Cited by 14 (Europe PMC)

PMID17324246PMCIDPMC2000606DOI10.1111/j.1365-2125.2007.02855.xPepBankPUB-17324246

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study8

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone8

In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Tesofensine.

01Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
In Alzheimer disease data, the NS2330 metabolite M1 had a modelled half-life of 374 h.
In plain wordsComputer analysis of Alzheimer disease data estimated a long half-life for M1, the tesofensine metabolite.
Peptide
Tesofensine
Outcome
Not applicableM1 elimination half-life
Study
n = 320
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Measurements
M1 half-life
374 h
Population model
Source sentences
Summary
Low apparent clearances together with large apparent volumes of distribution resulted in long half-lives of 234 h (NS2330) and 374 h (M1).
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424608
02Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
In Alzheimer disease data, one-compartment models with first-order elimination best described NS2330 and M1 concentration-time profiles.
In plain wordsComputer analysis of Alzheimer disease data described NS2330 and M1 concentrations with one-compartment models.
Peptide
Tesofensine
Outcome
Not applicableConcentration-time model
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Plasma concentration-time profiles of NS2330 and M1 were best described by one-compartment models with first-order elimination for both compounds.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424601
03Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
In Alzheimer disease data, a first-order process best modelled NS2330 absorption.
In plain wordsComputer analysis of Alzheimer disease data described NS2330 absorption with a first-order process.
Peptide
Tesofensine
Outcome
Not applicableAbsorption model
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Absorption of NS2330 was best modelled by a first-order process.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424602
04Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
In Alzheimer disease data, low apparent clearance and large distribution volume yielded an NS2330 half-life of 234 h.
In plain wordsComputer analysis of Alzheimer disease data estimated a long NS2330 half-life.
Peptide
Tesofensine
Outcome
Not applicableElimination half-life
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Measurements
NS2330 half-life
234 h
Population model
Source sentences
Summary
Low apparent clearances together with large apparent volumes of distribution resulted in long half-lives of 234 h (NS2330) and 374 h (M1).
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424603
05Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
In Alzheimer disease data, weight, sex, CL(CR), BMI and age influenced modelled NS2330 and/or M1 pharmacokinetics.
In plain wordsComputer analysis linked weight, sex, kidney clearance, BMI and age to NS2330 and/or M1 pharmacokinetics.
Peptide
Tesofensine
Outcome
Not applicablePharmacokinetic covariates
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
The covariate analysis identified weight, sex, CL(CR), BMI and age as influencing the pharmacokinetics of NS2330 and/or M1.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424604
06Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
Simulations found that only CL(CR) and sex significantly affected steady-state plasma concentration-time profiles of NS2330 and/or M1.
In plain wordsComputer simulations found significant effects of kidney clearance and sex on steady-state blood concentration profiles.
Peptide
Tesofensine
Outcome
Not applicableSteady-state profile covariates
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
However, simulations performed revealed that only CL(CR) and sex had a significant effect on the steady-state plasma concentration-time profiles.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424605
07Computer modelNot a test of Tesofensine aloneIn silicoPharmacokinetics
Modelled exposure was 62% higher in females with creatinine clearance of 35.6 ml min(-1) than males without renal impairment.
In plain wordsComputer analysis estimated higher exposure in females with reduced kidney clearance than in males without kidney impairment.
Peptide
Tesofensine
Outcome
IncreaseExposure by sex and renal function
Study
n: not reported in source
Population pharmacokinetic model
Comparator
Males without renal impairment
Outcome group
Pharmacokinetics · Pharmacology
Measurements
Exposure increase
62%
Females versus males without renal impairment
Creatinine clearance
35.6 ml min(-1)
Females
Source sentences
Summary
Females with a creatinine clearance of 35.6 ml min(-1) showed a 62% increased exposure compared with males without renal impairment.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424606
08Computer modelNot a test of Tesofensine aloneIn silicoOther
An external dataset supported the robustness and accuracy of the NS2330 and M1 model.
In plain wordsComputer analysis successfully predicted an external dataset with the NS2330 and M1 model.
Peptide
Tesofensine
Outcome
Not applicableExternal model prediction
Study
n: not reported in source
Population pharmacokinetic model
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
The robustness and accuracy of the model were demonstrated by the successful predictivity of an external dataset.
2 context sentences(design, population, supporting numbers)
Summary · context
To develop a population pharmacokinetic model for NS2330 and its major metabolite M1 based on data from a 14 week proof of concept study in patients with Alzheimer's disease, and to identify covariates that might influence the pharmacokinetic characteristics of the drug and/or its metabolite.
Summary · context
Plasma data from 320 subjects undergoing multiple oral dosing, and consisting of 1969 NS2330 and 1714 metabolite concentrations were fitted simultaneously using NONMEM.
In this study, Tesofensine was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tesofensine.
Report a problemFND-1732424607

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

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