high dose treatment
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2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.


2021 ◽  
Vol 14 ◽  
pp. 175628482110217
Author(s):  
Reidar Fossmark ◽  
Maya Olaisen ◽  
Tom Christian Martinsen ◽  
Hans Olav Melberg

Background: Oral 5-aminosalicylic acid (5-ASA) is the mainstay treatment of ulcerative colitis (UC) and therapy with oral 5-ASA is associated with beneficial outcomes. We have examined factors associated with the persistence of oral 5-ASA treatment in a national cohort of UC patients. Methods: Patients with newly diagnosed UC from 2010 to 2014 using oral 5-ASA monotherapy were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The median follow-up time was 1029 days. Drug persistence was defined as duration of oral 5-ASA preparation as monotherapy. Non-persistence of a oral 5-ASA preparation as monotherapy was defined as stopping oral 5-ASA, initiation of any further anti-inflammatory treatment including a course of glucocorticoids and a change to another oral 5-ASA preparation. Drug persistence was analyzed using the Kaplan–Meier method and influence of covariates on drug persistence was analyzed with the Cox proportional hazard model. Results: A total of 3421 patients were identified. The overall median 5-ASA drug persistence was 179 days. In univariate analyses, persistence was associated with preparation type and high-dose treatment, while oral glucocorticoid use or hospitalization around the start of oral 5-ASA were associated with shorter 5-ASA persistence. In multivariate analyses, oral glucocorticoids [HR 1.67 (1.54–1.80), p < 0.005] and hospitalization around start of 5-ASA [HR 1.23 (1.14–1.34), p < 0.005] were associated with non-persistence, whereas high dose (⩾3 g/day) 5-ASA was associated with longer persistence [HR 0.68 (0.65–0.71), p < 0.005]. Conclusion: High-dose treatment with oral 5-ASA was associated with longer persistence of oral 5-ASA monotherapy, whereas the presence of factors indicating more severe disease around initiation of 5-ASA monotherapy was associated with a shorter persistence.


2019 ◽  
Vol 9 (1) ◽  
pp. 71 ◽  
Author(s):  
Alina G. Liedtke ◽  
Sebastiano A. G. Lava ◽  
Gregorio P. Milani ◽  
Carlo Agostoni ◽  
Viola Gilardi ◽  
...  

Selective ß2-agonists have been imputed as potential cause of l-hyperlactatemia since the 1970s. To document the prevalence of hyperlactatemia associated with selective ß2-agonists and to investigate the predisposing factors, we searched for published articles until April 2019 pertaining to the interplay of administration of selective ß2-agonists and circulating l-lactic acid in the Excerpta Medica, Web of Science, and the U.S. National Library of Medicine databases. Out of the 1834 initially retrieved records, 56 articles were included: 42 papers reporting individual cases, 2 observational studies, and 12 clinical trials. Forty-seven individual patients receiving a selective ß2-agonist were found to have l-lactatemia ≥5.0 mmol/L, which decreased by ≥3.0 mmol/L or to ≤2.5 mmol/L after discontinuing (N = 24), reducing (N = 17) or without modifying the dosage of the selective ß2-agonist (N = 6). Clinical trials found that l-lactic acid significantly increased in healthy volunteers administered a ß2-agonist. l-lactatemia ≥5.0 mmol/L was observed in 103 (24%) out of 426 patients with asthma or preterm labor managed with a selective ß2-agonist and was more common in patients with asthma (30%) than in premature labor (5.9%). A significant relationship was also noted between l-lactate level and intravenous albuterol dose or its circulating level. In conclusion, relevant l-hyperlactatemia is common on high dose treatment with a selective ß2-agonist.


2019 ◽  
Vol 8 (12) ◽  
pp. 2109 ◽  
Author(s):  
Eriko Yasutomi ◽  
Sakiko Hiraoka ◽  
Shumpei Yamamoto ◽  
Shohei Oka ◽  
Mami Hirai ◽  
...  

Background and aim: Oral mesalazine and sulfasalazine (SASP) are key drugs for treating ulcerative colitis (UC). The efficacy of switching from one of the several mesalazine formulations to another is largely unknown. This study assessed the efficacy of switching among three types of mesalazine formulation and SASP for UC therapy. Methods: UC patients receiving high-dose mesalazine/SASP who switched to other formulations due to disease activity were considered eligible. Efficacy was evaluated 2, 6, and 12 months after switching. Results: A total of 106 switches in 88 UC patients were analyzed. The efficacy at 2 months after switching was observed in 23/39 (59%) cases from any mesalazine formulation to SASP, in 18/55 (33%) cases from one mesalazine to another, and in 2/12 (17%) cases from SASP to any mesalazine formulation. Nine of 43 effective cases showed inefficacy or became intolerant post-switching. Delayed efficacy more than two months after switching was observed in four cases. Steroid-free remission was achieved in 42/106 (39%) cases—within 100 days in 35 of these cases (83%). Conclusions: Switching from mesalazine to SASP was effective in more than half of cases. The efficacy of switching between mesalazine formulations was lower but may be worth attempting in clinical practice from a safety perspective.


2019 ◽  
Vol 31 (4) ◽  
pp. 537-545 ◽  
Author(s):  
Eric R. Burrough ◽  
Carson De Mille ◽  
Nicholas K. Gabler

Zinc oxide (ZnO) is commonly fed to pigs at pharmacologic concentrations (2,000–3,000 ppm) for the first 3 wk post-weaning to increase growth and reduce enteric bacterial disease. The safety of this high-dose treatment is assumed based upon lower bioavailability of ZnO compared to other common forms of Zn in feed; however, limited data are available regarding the specific serum and tissue concentrations of Zn expected in animals experiencing overload following feeding of excessive ZnO. Fifty-five 3-wk-old pigs were divided into 5 groups receiving various concentrations of ZnO (0–6,000 ppm) for 3 wk. Pigs receiving 6,000 ppm ZnO had higher mean pancreatic Zn concentrations ( p < 0.001) compared to other treatments, and higher pancreatic Zn concentrations were associated with pancreatic acinar cell apoptosis ( p < 0.0001). Hepatic Zn concentrations were highest for pigs receiving 6,000 ppm ZnO (mean ± SEM; 729 ± 264 ppm) and significantly higher than all other groups ( p < 0.0001), with controls having concentrations <60 ppm. Similarly, serum Zn was highest in pigs receiving 6,000 ppm ZnO (4.81 ± 2.31 ppm) and significantly higher than all groups (controls, <1 ppm). Additionally, as pigs became overloaded with Zn, there were significant reductions in serum Cu and both serum and hepatic Se. Hepatic and serum Zn concentrations >500 ppm and >2 ppm, respectively, are indicative of Zn overload, and dietary trace mineral analysis is warranted if expected inclusion rates are ≤3,000 ppm ZnO.


Nanomedicine ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. 1403-1427 ◽  
Author(s):  
Xiaolan Yin ◽  
Leiqiang Han ◽  
Shengjun Mu ◽  
Weiwei Mu ◽  
Shuang Liang ◽  
...  

2018 ◽  
Vol 22 (9) ◽  
pp. 991-999
Author(s):  
M. A. Zuur ◽  
A. D. I. van Asselt ◽  
N. van 't Boveneind-Vrubleuskaya ◽  
A. Aleksa ◽  
M. J. Postma ◽  
...  

2017 ◽  
Vol 25 (2) ◽  
pp. 119-123
Author(s):  
Rukhsana Quadir ◽  
Md Ismail Khan ◽  
Eliza Omar Eva ◽  
Hasanur Rahman ◽  
Faizul Ahasan ◽  
...  

The pathogenesis of gentamicin-induced nephrotoxicity has shown to generate oxygen free radicals. Several free radical scavengers are well recognized to ameliorate the nephrotoxicity. The seeds and oil of nigella sativa were reported to possess strong antioxidant properties and was effective against disease and chemically-induced hepatotoxicity and nephrotoxicity.The experiments were carried out in two parts, Experiment I and Experiment II, on a total of 35 rats of 8-12 weeks old and weighing between 200 and 230g. Nephrotoxicity and amelioration of nephrotoxicity was evaluated by measurement of concentrations of serum creatinine. The rats were induced nephrotoxicity by subcutaneous injection of gentamicin 100mg/kg/day for 9 days and were sacrificed on 10th day. The results indicated that gentamicin treatment caused marked renal tubular damage significant increase (P<0.001) of serum creatinine concentrations when compared to those of control.When n-hexane extract of N.sativa was administered as low and high dose with gentamicin and compared with the gentamicin treated groups, it was found that in these two groups there was significant decrease (P<0.001) of serum creatinine levels. When these two groups were compared with each other, it was observed that more amelioration occurred significantly in high dose treatment group than in the low dose treatment group. This study established that oral administration of n-hexane extract of N. sativa was able to produce considerable improvement from the nephrotoxic action of gentamicin in rats. The best amelioration was obtained in high dose treatment. Low dose treatment brought out the least amelioration of them all. Future works could better be directed towards obtaining the specific ingredient and the specific mechanism responsible for nephroprotection. We are hopeful that complete amelioration might not be impossible if given in proper doses or more effectively if we could extract the actual ingredients responsible for nephroprotection and can use them eventually.J Dhaka Medical College, Vol. 25, No.2, October, 2016, Page 119-123


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