Dataset Information

Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

ABSTRACT:

Background

Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

Methods

This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations were assessed, and microbiome changes were compared.

Results

Sixteen healthy volunteers with a mean age of 26 (standard deviation [SD], 5) years were enrolled; 62.5% were male, and participants' mean body mass index was 23.5 (SD, 4.0) kg/m2. Omadacycline was well tolerated with no safety signal differences between the 2 antibiotics. A rapid initial increase in fecal concentrations of omadacycline was observed compared to vancomycin, with maximum concentrations achieved within 48 hours. A significant difference in alpha diversity was observed following therapy in both the omadacycline and vancomycin groups (P < .05). Bacterial abundance and beta diversity analysis showed differing microbiome changes in subjects who received omadacycline versus vancomycin.

Conclusions

Subjects given omadacycline had high fecal concentrations with a distinct microbiome profile compared to vancomycin.

Clinical trials registration

NCT06030219.

SUBMITTER: Jo J

PROVIDER: S-EPMC10786255 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

Jo Jinhee J Hu Chenlin C Begum Khurshida K Wang Weiqun W Le Thanh M TM Agyapong Samantha S Hanson Blake M BM Ayele Hossaena H Lancaster Chris C Jahangir Alam M M Gonzales-Luna Anne J AJ Garey Kevin W KW

The Journal of infectious diseases 20240101 1

<h4>Background</h4>Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.<h4>Methods</h4>This was a phase 1, nonblinded, randomized clinical trial c ...[more]

PMID: 38051631

Similar Datasets

Project description:Dronabinol is a pharmaceutical tetrahydrocannabinol originally developed as an oral capsule. A dronabinol oral solution was recently approved, and the effects of food on absorption and bioavailability of the oral solution versus capsules were compared in an open-label, single-dose, 3-period crossover study. Healthy volunteers were randomized to either dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted). Dosing was separated by a 7-day washout period. Plasma pharmacokinetics were evaluated for dronabinol and its major metabolite, 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-?9-THC). Pharmacokinetic data were available for analysis in 54 volunteers. In the fed state, initial dronabinol absorption was faster with oral solution versus capsule (mean time to the first measurable concentration, 0.15 vs 2.02 hours, respectively), with 100% and 15% of volunteers, respectively, having detectable plasma dronabinol levels 30 minutes postdose. There was less interindividual variability in plasma dronabinol concentration during early absorption with oral solution versus capsule. Compared with the fasted state, mean area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t ) increased by 2.1- and 2.4-fold for dronabinol oral solution and capsule, respectively, when taken with food. Mean time to maximum plasma concentration was similarly delayed for dronabinol oral solution with food (7.7 hours) and capsule with food (5.6 hours) versus capsule with fasting (1.7 hours). Under fed conditions, AUC0-t and area under the plasma concentration-time curve from time zero to infinity were similar for the oral solution versus capsule based on 11-OH-?9-THC levels. An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients, given its rapid and lower interindividual absorption variability versus dronabinol capsule.

Dataset Information

Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Fecal Pharmacokinetics and Gut Microbiome Effects of Oral Omadacycline Versus Vancomycin in Healthy Volunteers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets