China 
Africa 
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Confessions from an insider
Published in Peter C. Gøtzsche, Richard Smith, Drummond Rennie, Deadly Medicines and Organised Crime, 2019
Peter C. Gøtzsche, Richard Smith, Drummond Rennie
The NSAID area is a horror story filled with extravagant claims, bending of the rules, regulatory inaction, and complacency with what the industry wants even though statements from industry scientists were often logically inconsistent or plainly wrong.22 Several drugs that were so kindly treated by the FDA were later withdrawn from the market because of their toxicity despite claims to the contrary, e.g. ‘Excellent gastrointestinal tolerance’ (benoxaprofen), ‘superior tolerance’ (indoprofen), ‘proven gastrointestinal safety’ (rofecoxib), ‘hurts the pain not the patient’ (ketorolac) and ‘least possible side effect profile’ (tolmetin).24 Sheer nonsense, as a least possible side-effect profile can only occur if you don’t take a drug at all. Other withdrawn drugs are, for example, zomepirac, suprofen and valdecoxib.22,26
Effects of Drugs
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
Mosher and Kircher (1988) examined proliferative lesions of the adrenal medulla in rats treated with zomepirac sodium. This nonsteroidal anti-inflammatory drug caused an increase in focal hyperplasia and benign medullary tumors in 24-month-old male rats. Zomepirac sodium can be added to the list of substances that have been associated with increased proliferative lesions in the adrenal medulla of the aged rat.
The influence of physicochemical properties on the reactivity and stability of acyl glucuronides†
Published in Xenobiotica, 2018
Patrick Camilleri, Akshay Buch, Brandi Soldo, Andrew J. Hutt
While the electronic and steric considerations, as discussed herein, may appear to be relatively simplistic such considerations have the potential to be of importance in drug design particularly in instances where conjugation with glucuronic acid is likely to be a major pathway of quantitative significance. Such considerations are exemplified by a consideration of zomepirac, a drug where in vivo conjugation with glucuronic acid is essentially quantitative; zomepirac was withdrawn due to toxicity. On the other hand, the structurally related drug tolmetin, where conjugation is a relatively minor pathway, and alternative metabolic routes, in particular oxidation, are quantitatively more significant than conjugation, is relatively safe and commercially available as a non-steroidal anti-inflammatory drug. However, it must be appreciated that quantitative comparisons between metabolic pathways may be problematic, particularly with respect to acyl glucuronide formation due to potential hydrolysis, either chemically or enzymatically mediated, may mask the significance of the pathway in vivo.
Species differences in liver microsomal hydrolysis of acyl glucuronide in humans and rats
Published in Xenobiotica, 2022
Hiroyuki Ikuta, Hiroaki Shimada, Kenjiro Sakamoto, Rena Nakamura, Atsushi Kawase, Masahiro Iwaki
Most AGs can be hydrolysed by enzymes, such as β-glucuronidase and some esterases (Smith et al. 1990; Spahn-Langguth and Benet 1992; Tanaka and Suzuki 1994; Brunelle and Verbeeck 1997). Among various esterases, both α/β hydrolase domain containing 10 (ABHD10), and acylpeptide hydrolase (APEH), were seen to serve as AG hydrolases (Suzuki et al. 2010; Iwamura et al. 2012). Iwamura et al. reported that zomepirac (ZOM), an NSAID, induces acute kidney injury as a result of elevated plasma, liver, and kidney ZOM-AG levels by the co-administration of an esterase inhibitor, tri-o-tolyl phosphate, in mice (Iwamura et al. 2016). The accumulation of AGs in tissues due to decreased AG hydrolase activity can be considered an IDT risk factor.