Mass Balance and Metabolite Profile after Single and Multiple Oral Doses of Pritelivir in Healthy Subjects

Abstract

Pritelivir is a helicase‐primase inhibitor active against HSV. Two human mass balance trials (a multiple‐dose trial and a single‐dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C‐pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half‐life of pritelivir was 63‐67 hours. Overall, 92% and 66% of the administered dose was recovered in the multiple and single dose trials, respectively. The low recovery after the single dose (66%) was most likely related to the formulation used. The major metabolic pathway was amide hydrolysis leading to amino thiazole sulfonamide (ATS) and pyridinyl phenyl acetic acid (PPA). In plasma, pritelivir, ATS, PPA, and PPA‐acyl glucuronide accounted for 40.6%, 9.4%, 5.1%, and 0.2% of total radioactivity. More than 90% of drug‐related material was eliminated 624 hours postdose. The majority was excreted in urine (75% and 77%), followed by feces (16% and 23%). The main components in urine were PPA‐acyl glucuronide (and its isomers), ATS, and its N‐demethylated isomers. Only minor metabolites were observed in feces. In conclusion, the major metabolic pathways of pritelivir have been identified with the primary excretion route being renal.

Development and validation of HPLC‐ultraviolet method for quantitative determination of pritelivir in human placental perfusion medium

“…In previous studies, the extraction of pritelivir from human plasma and urine samples was performed using the protein precipitation method with acidified methanol or acetonitrile (Biswas et al, 2014;Bonsmann et al, 2024;Quenelle et al, 2018). However, given the potential hydrolysis of the sulfamoyl group in sulfonamides (Białk-Bielińska et al, 2012), we decided against using acidic conditions in our method for processing of samples for HPLC analysis.…”

“…To the best of our knowledge, no study has reported a validated method for the quantitative determination of pritelivir in biological matrixes. A brief description of an LC-tandem mass spectrometry method for quantifying pritelivir in biological samples was provided by Quenelle et al (2018), Biswas et al (2014), and Bonsmann et al (2024). Chromatographic separation of the analytes was achieved by Zorbax Eclipse XDB-C 18 or Ascentis RP-Amide HPLC columns.…”