Can diarrhea affect the pharmacokinetics of racecadotril in neonatal calves?

This study was aimed to determine the pharmacokinetics of antisecretory-acting racecadotril, used in the treatment of diarrhea in humans and dogs, following oral administration in both neonatal calves with healthy and neonatal calves with infectious diarrhea. The study was carried out on a total of 24 Holstein calves (2-20 days), of which 6 were healthy and 18 were infectious diarrhea. Calves with infectious diarrhea were divided into 3 groups according to the infectious agent (Escherichia coli, Cryptosporidium parvum, and rotavirus/coronavirus). Racecadotril was administered orally at 2.5 mg/kg dose to calves. The plasma concentrations of racecadotril and its main active metabolite (thiorphan) were determined using HPLC-UV. The pharmacokinetic parameters were analyzed using the non-compartmental method. In healthy calves, the t1/2ʎz , Cmax , Tmax, and AUC0-12 of racecadotril were determined 4.70 h, 377 ng/ml, 0.75 h, and 1674 h × ng/ml, respectively. In the plasma of calves with infectious diarrhea, racecadotril and thiorphan were only detected at the sampling time from 0.25 to 1.5 h. As in calves with infectious diarrhea, thiorphan in plasma was only detected in healthy calves from 0.25 to 1.5 h. Racecadotril showed a large distribution volume, rapid elimination, and low metabolism to thiorphan in healthy calves.

[Gastroenterological symptoms in COVID-19 patients with mild severity of the disease: opportunities to optimize antidiarrheal therapy].

BACKGROUND: The novel coronavirus infection COVID-19 can be manifested by damage to the organs of the gastrointestinal tract (GIT). Damage to the gastrointestinal tract by the SARS-CoV-2 virus leads to a violation of the microbial-tissue complex of the mucous membrane of the digestive tract. A common gastroenterological manifestation of COVID-19 is diarrhea. AIM: Study of the clinical features of gastroenterological disorders and the possibility of optimizing the treatment of diarrheal syndrome in patients with COVID-19 with a mild form of viral infection. MATERIALS AND METHODS: The observation group consisted of 230 patients with mild COVID-19: K-group (n=115) with respiratory symptoms, I group (n=115) with gastrointestinal manifestations in combination and without signs of respiratory damage. In order to compare the effectiveness of treatment of diarrheal syndrome, patients of group I are randomized into 2 subgroups: Ia (n=58) prebiotic treatment (Zacofalk) and Ib (n=57) enterosorbents. RESULTS: The development of gastrointestinal symptoms with SARS-CoV-2 infection is significantly more often noted in comorbid patients (67%). Gastrointestinal symptoms were dominated by diarrhea (93.9%) and flatulence (76.5%), in 1/3 of patients they were the first manifestos of infection. It was established that in 98.4% of patients of group I (against 42.6% of the K-group) signs of infectious intoxication were detected. In patients with gastrointestinal lesions, an elongation of the febrile period by 91.5 days was noted, a later (6 days) verification of the viral etiology of the disease. It was found that in patients of group I, the regression of clinical symptoms, the duration of viral disease, the dynamics of antibody formation, the prognosis for the development of IBS-like disorders in the post-infectious period depended on the treatment. In patients taking (Zacofalk), these indicators were significantly better. CONCLUSION: In mild cases, to reduce the severity of viral intestinal damage, for effective relief of intestinal symptoms, to reduce the risk of IBS-like symptoms, it is advisable to prescribe (Zacofalk) in an initial dose of 3 tablets per day.