FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2122783187> ?p ?o ?g. }

• W2122783187 abstract "Dear Editor-in-Chief:I read with interest a recently published article in your esteemed journal by Lavasani et al., entitled “Study of the pharmacokinetic changes of Tramadol in diabetic rats” [1]. Lavasani et al., have evaluated the influence of full-blown diabetes on the pharmacokinetic disposition of tramadol using a rat model of diabetes mellitus induced by streptozotocin (DMIS) [1]. Since tramadol has been independently confirmed to have glucose lowering potential in DMIS [2] and as well being investigated for its role in alleviating pain in diabetic neuropathy [3,4], this pharmacokinetic investigation in DMIS was time appropriate. The design of the study also incorporated the assessment of the role of hepatic function via a perfused liver protocol [1]. The measurements of key circulating metabolites [M1, M2 and M5] along with tramadol provided the necessary data required for the assessment of the role of diabetes on the disposition of tramadol [1].The results of this investigation unequivocally confirmed that the exposure of tramadol increased substantially (approximately 4-fold) in diabetic rats with an identical 4-fold reduction in the oral clearance [1]. Also, the elimination rate constant for tramadol was reduced by about 1.5 fold in diabetic rats [1]. In terms of metabolites of tramadol, with the exception of M5 which showed similar exposure in diabetic vs control rats, the exposure of both M1 and M2 were about 1.42 to 1.76 fold greater in diabetic rats [1]. The perfused rat liver experiment suggested that both M1 and M5 were being formed in relatively higher amounts in diabetes rats vs control rats. Interestingly, the metabolite to parent ratio computation of diabetes rats vs control rats suggested that diabetes rats had a lower ratio in spite of higher turnover of metabolites by DMIS rat liver vs control rat liver [1]. The authors have provided interesting views to explain the observed findings of tramadol disposition in the diabetes rats that included lower volume of distribution and protein binding to account for higher tramadol exposure and possible CYP induction for the increased M1 level [1].The intent of this note is to provide additional clues to further tease out the observed findings of tramadol disposition in diabetes rats. Although shift in volume of distribution can alter exposure, perhaps, the decreased total body clearance is the key driver to explain the exposure increase for both tramadol and the metabolite M1. The disposition of tramadol is governed by efficient hepatic clearance and renal excretion of both the parent and the major oxidative metabolites (inclusive of M1) [5]. However, in diabetes rats the renal handling system is severely handicapped [6,7] and therefore, impaired renal excretion of tramadol and M1 can lead to increased systemic exposure. It appeared that impaired renal elimination of tramadol in DMIS rat model may explain the increased bioavailability observed in diabetes rats. The impaired renal elimination would also explain the time dependent increased build-up of the tramadol exposure in diabetes rats relative to control rats (Figure one; Lavasani et al.). However, unlike the parent, the effect of renal impairment on M1 appeared to have been more pronounced post 1 h after dosing (Figure one; Lavasani et al.) because there is a lag time for the hepatic formation of the metabolite. Nevertheless, renal impairment appeared to be an important contributor for the increased exposure of M1 in diabetes rats.In conclusion, the interesting work of Lavasani et al., has thrown some new light on the importance of well-planned experiments to tease out the variables that account for pharmacokinetic disposition of tramadol in diabetes rats [1]. The suggested work of intravenous dosing of tramadol in diabetes rats vs control rats will help in further elucidating the proposed mechanisms to explain the altered pharmacokinetic disposition of tramadol in diabetes rats [1]. However, it is strongly recommended that urinary excretion rate and renal clearance is also measured in this planned work to unequivocally establish the relationship of renal impairment on the disposition of tramadol and its metabolites in diabetes rats. Since tramadol is also excreted unchanged in humans along with the active M1 metabolite [8,9], the planned work is relevant to get dosing guidance of tramadol in patients." @default.
• W2122783187 created "2016-06-24" @default.
• W2122783187 creator A5056704911 @default.
• W2122783187 date "2013-03-15" @default.
• W2122783187 modified "2023-10-09" @default.
• W2122783187 title "Commentary on: “study of the pharmacokinetic changes of tramadol in diabetic rats” is the handicapped renal pathway in DMIS contributing for the increased bioavailability of tramadol?" @default.
• W2122783187 cites W2089072175 @default.
• W2122783187 cites W2112472910 @default.
• W2122783187 cites W2139211751 @default.
• W2122783187 cites W2148051963 @default.
• W2122783187 cites W2165140611 @default.
• W2122783187 cites W2167917925 @default.
• W2122783187 doi "https://doi.org/10.1186/2008-2231-21-23" @default.
• W2122783187 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3602013" @default.
• W2122783187 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23497476" @default.
• W2122783187 hasPublicationYear "2013" @default.
• W2122783187 type Work @default.
• W2122783187 sameAs 2122783187 @default.
• W2122783187 citedByCount "1" @default.
• W2122783187 countsByYear W21227831872014 @default.
• W2122783187 crossrefType "journal-article" @default.
• W2122783187 hasAuthorship W2122783187A5056704911 @default.
• W2122783187 hasBestOaLocation W21227831871 @default.
• W2122783187 hasConcept C112705442 @default.
• W2122783187 hasConcept C126322002 @default.
• W2122783187 hasConcept C134018914 @default.
• W2122783187 hasConcept C181389837 @default.
• W2122783187 hasConcept C2779280383 @default.
• W2122783187 hasConcept C2779777798 @default.
• W2122783187 hasConcept C2780820201 @default.
• W2122783187 hasConcept C42219234 @default.
• W2122783187 hasConcept C555293320 @default.
• W2122783187 hasConcept C71924100 @default.
• W2122783187 hasConcept C98274493 @default.
• W2122783187 hasConceptScore W2122783187C112705442 @default.
• W2122783187 hasConceptScore W2122783187C126322002 @default.
• W2122783187 hasConceptScore W2122783187C134018914 @default.
• W2122783187 hasConceptScore W2122783187C181389837 @default.
• W2122783187 hasConceptScore W2122783187C2779280383 @default.
• W2122783187 hasConceptScore W2122783187C2779777798 @default.
• W2122783187 hasConceptScore W2122783187C2780820201 @default.
• W2122783187 hasConceptScore W2122783187C42219234 @default.
• W2122783187 hasConceptScore W2122783187C555293320 @default.
• W2122783187 hasConceptScore W2122783187C71924100 @default.
• W2122783187 hasConceptScore W2122783187C98274493 @default.
• W2122783187 hasLocation W21227831871 @default.
• W2122783187 hasLocation W21227831872 @default.
• W2122783187 hasLocation W21227831873 @default.
• W2122783187 hasLocation W21227831874 @default.
• W2122783187 hasOpenAccess W2122783187 @default.
• W2122783187 hasPrimaryLocation W21227831871 @default.
• W2122783187 hasRelatedWork W1572093353 @default.
• W2122783187 hasRelatedWork W1595471877 @default.
• W2122783187 hasRelatedWork W1982544589 @default.
• W2122783187 hasRelatedWork W2001695800 @default.
• W2122783187 hasRelatedWork W2004106975 @default.
• W2122783187 hasRelatedWork W2034147284 @default.
• W2122783187 hasRelatedWork W2051523080 @default.
• W2122783187 hasRelatedWork W2065209479 @default.
• W2122783187 hasRelatedWork W2080103183 @default.
• W2122783187 hasRelatedWork W2084942104 @default.
• W2122783187 hasRelatedWork W2104689512 @default.
• W2122783187 hasRelatedWork W2129326750 @default.
• W2122783187 hasRelatedWork W2149520032 @default.
• W2122783187 hasRelatedWork W2330871695 @default.
• W2122783187 hasRelatedWork W2359734707 @default.
• W2122783187 hasRelatedWork W2414438736 @default.
• W2122783187 hasRelatedWork W2415703365 @default.
• W2122783187 hasRelatedWork W3082154885 @default.
• W2122783187 hasRelatedWork W602281557 @default.
• W2122783187 hasRelatedWork W2539073332 @default.
• W2122783187 isParatext "false" @default.
• W2122783187 isRetracted "false" @default.
• W2122783187 magId "2122783187" @default.
• W2122783187 workType "article" @default.