Latest News


Shire used 14C + AMS to determine the PK, absorption and excretion of revexepride in a Phase I clinical trial

October 5, 2016

“In the last decade, the administration of reduced doses of 14C-labeled compounds (typically 0.2-1 µCi) combined with AMS has enabled quantitative absorption, metabolism and excretion (AME) studies to be conducted in place of traditional scintillation counting-based studies.  The very low doses of radioactivity used in these studies minimize potential safety and regulatory concerns around the use of radioactive material in clinical trials.”

“This study demonstrated that revexepride was rapidly absorbed and exhibited an appreciable level of oral absorption.  Almost 100% of total radioactivity was recovered in the urine (mean, 38.2%)and feces (mean, 57.3%) of participants, indicating that these were the major routes of excretion.”

The paper may be accessed here

 

Amgen used LC+AMS during determination of Pharmacokinetics, Biotransformation, and Excretion of [14C]Etelcalcetide (AMG 416) Following a Single Microtracer Intravenous Dose in Patients with Chronic Kidney Disease on Hemodialysis

August 15, 2016

“Accelerator mass spectrometry was necessary to measure the microtracer quantities of C-14 excreted in the large volumes of dialysate and other biomatrices. An estimated 67 % of the [14C]etelcalcetide dose was recovered in dialysate, urine, and feces 176 days after dose administration. Etelcalcetide was primarily cleared by hemodialysis, with approximately 60 % of the administered dose eliminated in dialysate. Minor excretion was observed in urine and feces.”

“A therapeutic dose was administered that contained a microtracer quantity of [14C]etelcalcetide in order to limit patient exposure to C-14 and to facilitate study conduct in a dialysis clinic. The microtracer approach necessitated using accelerator mass spectrometry (AMS) to achieve the sensitivity required for quantification of the low concentrations of radioactivity excreted in the large volumes of dialysate and other biomatrices over the long study duration.”

“Higher quantities of C-14 more typical for human drug disposition studies were considered but not pursued because of the difficulty in controlling radioactivity contamination if hospitalizations were required during the study. One patient required hospitalization, and microtracer labeling obviated the need for contamination controls. The microtracer approach required the use of AMS for C-14 measurement in biofluids and dialysate. Remarkable detection limits were enabled by AMS, with C-14 concentrations of approximately 0.25 mBq (approximately 6.7 fCi/g) of 14C (approximately 0.06 ng equivalents of etelcalcetide/g) quantified in an approximately 0.35 g dialysate sample prepared from approximately 150 kg of dialysate collected on study day 176.”

The paper may be downloaded from the link here

 

 

UCB used LC+AMS in the determination of Pharmacokinetics and Metabolism of [14C]-Tozadenant (SYN-115), a Novel A2a receptor antagonist ligand, in Healthy volunteers

August 12, 2016

Due to the low amount of radioactivity anticipated in plasma and in excreta, which were likely to be below the levels that can be reliably measured by liquid scintillation counting (LSC), AMS was also used for plasma, whole blood, urine and feces determinations. Subsequently, metabolic profiles of tozadenant in plasma, urine and feces were determined in pooled samples, using HPLC fractionation followed by AMS analysis in fractions.

The human pharmacokinetics, mass balance and metabolite profiling of tozadenant were successfully characterized.

The only identified species circulating in plasma determined by HPLC+AMS was unchanged tozadenant amounting to approximately 93% of plasma radioactivity in two subjects.

The radiocarbon excretion recovery was approximately 86%, of which 55% fecal and 31% was urinary excretion, respectively. The cumulative excretion of unchanged tozadenent was approximately 30% of the dose (11% in urine and 19% in feces), consistent with the extensive biotransformation of tozadenant through multiple pathways. Fifteen metabolites were identified by their mass fragmentation patterns.

An accepted author version of the paper is available here

 

New AstraZeneca study with AMS – Metabolic Disposition of Osimertinib in Rats, Dogs and Humans: Insight into a Drug Designed to Bind Covalently to a Cysteine Residue of Epidermal Growth Factor

August 4, 2016

Download the publication from here

 

New Roche publication – Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects

June 9, 2016

Retrieve the publication from here

 

AstraZeneca – Incorporation of an IV [14C]-microtracer dose into a first in human study to determine the absolute oral bioavailability of AZD5122

May 18, 2016

Retrieve the paper from here

 

Taiho prodrug TAS-102 – PK, excretory pathways and metabolism determined in patients with advanced solid tumors using HPLC plus AMS

March 24, 2016

Get the paper from Cancer Chemotherapy and Pharmacology here

TAS-102 was approved in America in 2015 as Lonsurf®.

 

 

A guide to transferring and validating quantitative analytical methods for LC+AMS

October 28, 2015

This white paper describes why LC or LC-MS/MS methods must be carefully evaluated as they are adopted for LC+AMS use and why the resultant LC+AMS method must be fully validated before use.  A three-batch validation is the only way to ensure method reproducibility and deliver LC+AMS data reliably.

Download here

 

Xceleron latest presentation – The successful application of carbon isotopes in preclinical and clinical pharmaceutical research

October 6, 2015

Presented at the 21st Workshop on the Synthesis and Applications of Isotopes and Isotopically Labelled Compounds, International Isotope Society-Central European Division, Bad Soden, Germany

Download the presentation from here

 

Xceleron Webinar – Genentech and GSK discuss microtracer use

September 16, 2015

Successful Clinical [14C] Microtracer Investigations – Case Studies from GSK and Genentech

Thursday, 24th September 2015 at 11:00 am EDT – 12:00 pm EDT

Go here to pre-register for the webinar

 

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