Case description: Oxybutynin can induce elevation in liver enzymes; Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST). We describe a case of 49-year old male patient who presented to an emergency department (ED) with right side weakness and inability to speak. He was diagnosed with stroke and admitted to Qatar Rehabilitation Institute (QRI) after the acute management course at Hamad General Hospital (HGH). As part of his management, he was started on (oxybutynin 5 mg orally twice daily) for overactive bladder. Within a week his liver enzymes started to increase and after a thorough medication review, oxybutynin was suspended as it was the only suspected medication to be responsible for this adverse drug reaction (ADR). This ADR was classified as “probable” due to oxybutynin using the Naranjo Adverse Drug Reaction scale.Conclusion: This is the first published report on oxybutynin induced elevation in liver enzymes. Further reports are required to confirm this probable ADR and alert all health professionals about it.
PH46A is the lead of a new class of bioactive indanes with potential for the treatment of inflammatory bowel disease. A qualitative in vitro metabolism profile of PH46A was investigated in preclinical studies, and the rate of its metabolism in cryopreserved hepatocytes prepared from male Sprague Dawley rat, Beagle dog, Cynomolgus monkey and pooled mixed gender human was compared by LC-MS. The clearance order of PH46A was determined to be rat>dog>monkey>human. The species tested which exhibited the closest clearance values to the human was monkey. Following incubation of PH46A with cryopreserved hepatocytes, 5 metabolites were identified, including M1 (keto-PH46), M2 (PH46-OH, PH132), M3 (PH46-diOH), M4 (keto-glucuronide-PH46) and M5 (glucuronide conjugate-PH46). It was found that the human metabolites M2 and M5 were also present in rat, dog and monkey, while M1 was present in all species except monkey. M2 was detected in dog and monkey by LC1 conditions, but only in dog by LC2. Therefore, the metabolism in rat was most similar to human, in terms of the metabolites observed, but all putative human metabolites were present in rat and dog. We further explored the characterization of key metabolite M2 (PH46-OH). Identical PH46-OH was obtained via a bio-catalytic oxidation method from PH46 using rat liver microsomes (RLM) and the human liver P450s (Cyp2D6, Cyp 2C19 and Cyp 4A11) following screening of selectAZyme panels of microbial P450s, recombinant human liver P450s and different microsomes. RLM was used in scale up production and PH132 was isolated and characterized as 4-(((1’S,2’S)-1’,6-dihydroxy-1’,3’-dihydro- 1H,2’H-[2,2’-biinden]-2’-yl)methyl) benzoic acid via LC-MS/MS, NMR and HRMS. The site of hydroxylation on the biindane scaffold was unexpected. The outcomes of these studies have provided valuable information for future pharmacokinetic and in vivo toxicological investigations.
Background The global emergence and spread of extended-spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae have been threatening the ability to treat an infection. Hence, this study aimed to determine the prevalence of ESBL-producing and multi-drug resistance (MDR) Enterobacteriaceae (ESBLs-E) from different clinical specimens in Addis Ababa, Ethiopia. Methods A cross-sectional study was conducted from January 1 to May 30, 2017. A total of 426 Enterobacteriaceae isolates were identified from clinical specimens. The isolates were collected from four laboratories. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method on Muller Hinton agar (MHA). All Enterobacteriaceae were screened for ESBLs production using cefotaxime and ceftazidime as per CLSI guideline. Each ESBL screening positive Enterobacteriaceae were confirmed by a combination disk test (CDT). Data were entered and analyzed by using SPSS version-20. Result The most frequent Enterobacteriaceae were E. coli 228 (53.5%) and K. pneumoniae 103 (24.1%). The magnitude of ESBLs-E was 57.7% (246/426). The highest frequencies of ESBLs-E were observed in blood specimesns (84.4%) and the highest ESBLs production was observed in K. pneumoniae (85.4%). The highest resistance level was seen to sulfamethoxazole-trimethoprim (77.0%), amoxicillin with clavulanic acid (71.6%), cefotaxime (62.2%), cefepime (60.3%) and ceftazidime (60.8%). The overall magnitude of multi-drug resistance (MDR) level was 68.3%. Of ESBLs-E, 96.3% of them were MDR ( P < 0.001). Conclusion There was a high prevalence of ESBLs-E and MDR isolate in Addis Ababa. Most of ESBLs-E was isolated primarily in blood and urine. The highest ESBLs production was observed among K. pneumoniae . Hence, strong infection control strategies must be implemented in hospital settings of the country.
