(T1430-02-11) The Impact of Advanced Age on Bacterial Drug Degradation in the Lower Intestine and the Usefulness of Data in Fecal Material

Purpose: Estimate bacterial degradation rate constants of metronidazole and olsalazine in the lower intestine (distal ileum and proximal colon) of older people both in the fasted and in the fed state and compare with published data in healthy adults (Karatza et al. 2017). Estimate bacterial degradation rate constants of metronidazole and olsalazine in fecal material of older people and of healthy adults and evaluate differences with those in the lower intestine of older people (this study) and healthy adults (Karatza et al. 2017).

Methods: First-order degradation rate constants of metronidazole and olsalazine in the distal ileum and in the proximal colon of eight older people (65-71 years old) were estimated ex vivo using samples which had been collected under fasting conditions (fasted state) and 5 hours after the standard high-calorie, high-fat administered in the BA/BE studies (fed state) (Vertzoni et al. 2021). First-order degradation rate constants of metronidazole and olsalazine in fecal materials prepared from twelve older people (65-91 years old) and from six healthy adults (19-36 years old) were estimated. First-order degradation rate constants of metronidazole and olsalazine in fecal materials from additional six healthy adults (28-57 years old) were extracted from Karatza et al (2016). All degradation experiments were (or had been) performed under anaerobic conditions and according to established procedures (Karatza et al. 2016; Karatza et al. 2017).

Results: For metronidazole, first-order degradation rate constants in the contents of distal ileum and in the contents of proximal colon of older people were in line with values in healthy adults both in the fasted state and in the fed state. The first – order rate constants in fecal material prepared from individuals in advanced age and from healthy adults also did not differ significantly. However, in all comparisons data variability was high. For olsalazine, data in the distal ileum of older people were not collected due to unavailability of material. In contents of proximal colon of older people, the mean first – order degradation rate constant was significantly higher than in healthy adults, both in the fasted state and in the fed state. The first-order degradation rate constants in fecal material from older people and from healthy adults did not differ significantly, however, data variability was high.

Conclusion: Based on data collected in this study with metronidazole and olsalazine (1) the impact of advanced age on bacterial drug degradation in the lower intestine seems to be drug specific and (2) the usefulness of data in fecal material in evaluating age related bacterial drug degradation differences in the lower intestine is unclear, due to high data variability.

References: Karatza E, Vertzoni M, Muenster U, Reppas C. The Impact of Handling and Storage of Human Fecal Material on Bacterial Activity. J Pharm Sci. 105:3458-3461 (2016).
Karatza E, Goumas C, Muenster U, Reppas C, Vertzoni M. Ex vivo evaluation of degradation rates of metronidazole and olsalazine in distal ileum and in cecum: The impact of prandial state. Int J Pharm. 534:237-241 (2017).
Vertzoni M, Sulaiman S, Goumas K, Kersten E, Anlahr J, Muenster U, Reppas C. Characteristics of Contents of Lower intestine in the 65-74 Years of Age Range Could Impact the Performance of Safe and Efficacious Modified Release Products. J Pharm Sci. 110:251-258 (2021).