1Health Biology Research Lab (HBRL), Department of Physiology, Government College University, Faisalabad, Pakistan
Abstract
The gut microbiome potentially modulates pharmacokinetics of orally administered drugs. Homologous transporting proteins in epical membrane of the enterocytes and cell membrane of the residing microbial cells of the host may compete for absorption of the orally administered drugs. Microbial cells residing the small intestine of the host may uptake/bio-accumulate some of the quantity of the dose of orally administered drug. This project is aimed to observe absorption/bio-accumulation behavior of enalapril by the gut microbiome when enalapril was administered orally in pure form and in the presence of excipients (Tablet; commercial preparation). Currently, no data confirms specific transport system for enalapril uptake by gut microbiome in absence and presence of excipients as well. Two in-vivo trials, enalapril pure drug treated trial and enalapril commercial tablet treated trial were conducted in parallel. Each trial was conducted in adult Wistar albino rats (n=42) divided into seven groups having same number of rats in each group (n=6); one control group and six drug treated groups administered orally with single dose of enalapril 10mg/kgbwt. Rats (n=6) were subsequently sacrificed at different intestinal transit times of 1, 2, 3, 4, 5 and 6 hours post drug administration to harvest microbial mass pellet from digesta. Pellet was lysed to expose microbial lysate and pursued through HPLC. The microbiome absorbed enalapril at 4hour transit time (103±7.31µg) significantly (p≤0.05) higher as compared to 5hour transit time (73.2±5.17µg). Percent dose recovery from microbiome was significantly (p≤0.05) higher at 4hour transit time (4.15±0.05%) as compared to 5hour transit time (3.14±0.18%) post drug administration. Independent of presence of excipients, from both formulations enalapril was absorbed in equal amount competitively by the intestinal microbiome through the homologous transport mechanism present in the enterocytes of the host. Conclusively, enalapril serves as a substrate of gut microbiome independent of dosage form when administered orally.
Keywords: Enalapril, Microbiome, Microbial lysate, Percent drug recovery
