Pharmacokinetics of a novel trioxane antimalarial drug 99/411: alterations upon rifampicin coadministration, single and multiple oral dose drug–drug interactions in Sprague-Dawley rats

2017 ◽  
Vol 2 (4) ◽  
pp. 225-232
Author(s):  
Mahendra Kumar Hidau ◽  
Yeshwant Singh ◽  
Shio Kumar Singh
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Liang ◽  
Jing Ma ◽  
Bo Wei

AbstractTo investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.


2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Al-Qaraghuli AMS ◽  
Abdel Wahab EMN ◽  
Al-Ani IM ◽  
Faisal GG

Introduction: Xiang Sha Yang Wei Wan (XSYWW) is a Chinese traditional medicine that is used for gastrointestinal disorders, specifically gastric ulcer in many countries of South-East Asia. The aim of the study was to evaluate the potential effects of XSYWW on ethanol-induced gastric ulcer in rats by means of histological Study. On a similar basis of treatment, ranitidine, a conventional medication was used as gold standard. Methods: Fifty five male Sprague-Dawley rats (250-300 gm) were divided into four groups. Group I (ethanol treated group) was the control group and gastric ulcers were induced by administering 100% ethanol (1 ml/200 g). Group II (Pre-treatment group) was divided into two subgroups; they were orally fed with 1.0 gm/kg and 2.0 gm/kg respectively of XSYWW solution. Thirty minutes later they were administered with absolute ethanol as in group I. Group III, was given an oral dose of 2gm/kg of XSYWW solution after one hour of ethanol administration. Group IV was given an oral dose of 200mg/kg ranitidine solution after one hour of ethanol administration. Five rats from groups I, III and IV were sacrificed on day 1, 2 and 3 while the animals of group II were sacrificed one hour after ethanol administration. Results: Histological study of the stomachs from ethanol treated rats showed multiple ulcers of various depths that reached the muscularis and the serosa. Conclusion: Pre or post-treated rats with XSYWW showed that XSYWW has protective effect against ethanol-induced gastric mucosal lesion. However, there was a faster and more complete healing process in the ranitidine treated group when compared to the XSYWW treated subjects.


2018 ◽  
Vol 26 (2) ◽  
pp. 157-169
Author(s):  
Jong Hyun Nho ◽  
Jong Choon Kim ◽  
Hyun Woo Cho ◽  
Mu Jin Lee ◽  
Ho Kyung Jung ◽  
...  

2020 ◽  
Vol 14 (4) ◽  
pp. 193-200
Author(s):  
Mohammad Jamalian ◽  
◽  
Hassan Solhi ◽  
Parisa Ghasemi ◽  
Ali Rahbari ◽  
...  

Background: Paraquat poisoning results in multi-organ failure, primarily pulmonary fibrosis, acute renal failure, and hepatic impairment. The present study was designed to evaluate three treatment regimens, such as N-Acetyl cysteine (NAC), silymarin and hydrocortisone in the prevention of lung fibrosis after ingestion of toxic doses of paraquat in rats.  Methods: Male Sprague-Dawley rats (N=20) were randomly divided into four groups of five each. The drugs and paraquat were given to the rats orally. All rat groups received one oral dose of paraquat (10 mg/kg) once daily for 1 week. The first group received a daily oral dose of silymarin (600 mg/kg) for 2 weeks. The second group received a daily oral dose of NAC (500 mg/kg) for 2 weeks. The third group was given daily oral doses of NAC (500 mg/kg) and hydrocortisone (50 mg/kg) for 2 weeks. The fourth group (controls) received no drugs other than paraquat. The experiment continued for 4 weeks. After the experiment, autopsy was performed on all rats and the lungs were examined histopathologically. Results: The results of histopathology examinations for peribronchial inflammation in the groups were shown that NAC plus hydrocortisone and silymarin had notable effects in the prevention of lung inflammation. Septal widening in the lungs was also observed in group three less than that in the other groups. Conclusion: Based on the results, silymarin, NAC and hydrocortisone may be used as a palliative treatment in paraquat poisoning specifically aimed at preventing the acute and chronic lung injuries as the worst complication of the poisoning.   


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
S. Antwi ◽  
J. Asiedu-Larbi ◽  
O. N. K. Martey ◽  
O. Quasie ◽  
M. Boakye-Yiadom ◽  
...  

Mist Antiaris is a herbal decoction for treatment of nervous disorders. Safety and efficacy were evaluated in Sprague-Dawley rats and human patients, respectively. Acute toxicity was assessed by administration of a single 5000 mg/kg oral dose of decoction to a group of six rats. For subchronic toxicity, four groups of six rats each received water (control) or 10, 100, or 200 mg/kg oral doses of decoction daily for eight weeks. Body weight, serum, urine, and hematological profile of the animals in each group were monitored over the period. Effects of treatment on pentobarbital-induced sleeping time and histology of liver, lung, heart, and kidney tissue were assessed at the end of the study. There was no evidence of acute toxicity within 48 hours of the oral dose. Over the 8-week period, body weight increases in Mist Antiaris treatment groups were reduced relative to the control group. There were no significant differences in urine profile, serum biochemistry, hematological parameters, and pentobarbital-induced sleeping time. Tissue histology revealed no differences relative to controls. Assessment of efficacy was by retrospective review of data on patients who presented with peripheral neuropathy. Treatment resulted in 53.7 % of patients reporting complete resolution and 15.7 % showing reduction in neuropathic symptoms. The data demonstrate that there is no toxicity due to subchronic administration of Mist Antiaris in Sprague-Dawley rats. The reduction or resolution of neuropathic symptoms indicated by patents’ file data provides evidence to suggest that Mist Antiaris has antineuropathic effects.


2002 ◽  
Vol 21 (11) ◽  
pp. 599-605 ◽  
Author(s):  
S W Borron ◽  
C Monier ◽  
P Risède ◽  
F J Baud

Opiates and substitution products are frequently abused, alone and in association with benzodiazepines. While this combination may result in severe respiratory depression and death, the quantitative relationship remains uncertain. We performed randomized, blinded intravenous median lethal dose (MLD) studies in Sprague–Dawley rats of morphine, buprenorphine, and methadone, alone and in combination with intraperitoneal flunitrazepam pretreatment. We employed the up-and-down method, performed in quadruplicate, comparing time to death following opioid injection. Results are expressed as median of four series (extremes). The MLDs of morphine, buprenorphine, and methadone alone were 64.0 (33.6:79.5), 234.6 (168.6:284.4), and 22.5 (19.3:24.1) mg/kg, respectively, and 60.6 (35.2:88.2), 38.4 (30.6:54.0), and 13.0 (9.7:13.8) mg/kg, respectively, after pretreatment with 40 mg/kg flunitrazepam. Times to death for morphine, buprenorphine, and methadone alone were 2.5 (0.8:24), 0.02 (0.0:24), and 2.0 (0.0:24) hours, respectively, and 13.5 (0.0:144), 24.0 (0.0:120), and 0.0 (0.0:24) hours, respectively, after pretreatment with flunitrazepam 40 mg/kg, ip. Flunitrazepam significantly altered methadone (P=0.02) and buprenorphine (P=0.02) but not morphine lethality (P=0.77). Flunitrazepam significantly prolonged time to death only for buprenorphine (P<0.01). Flunitrazepam–opioid drug–drug interactions are more complex than is generally believed. Mechanistic studies of flunitrazepam–opioid lethal interactions are needed.


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