Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins

Herman, Robert J.; Chaudhary, Archana; Szakacs, Cameron; Woo, Dong Hun; Lane, Rosalie A.; Boctor, M. A.

doi:10.1007/bf00198307

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…Vree et al [35] showed that, despite the different concentrations of temazepam glucuronide and oxazepam glucuronide diastereoisomers, there was no difference in the half-lives between the respective diastereoisomers. Extrahepatic glucuronidation, enterohepatic recirculation, [36,37] and enzymatic systems may cause the inversion of one enantiomer to another, [38] and plasma protein binding [35] may also contribute to stereoselective metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolites of lorazepam: Relevance of past findings to present day use of LC‐MS/MS in analytical toxicology

Turfus¹,

Braithwaite²,

Cowan³

et al. 2011

Drug Testing and Analysis

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The advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the sensitivity it confers, permits the analysis of both phase I and II drug metabolites that in the past would have been difficult to target using other techniques. These metabolites may have relevance to current analytical toxicology employing LC-MS/MS, and lorazepam was chosen as a model drug for investigation, as only the parent compound has been targeted for screening purposes. Following lorazepam administration (2 mg, p.o.) to 6 volunteers, metabolites were identified in urine by electrospray ionization LC-MS/MS, aided by the use of deuterated analogues generated by microsomal incubation for use as internal chromatographic and mass spectrometric markers. Metabolites present were lorazepam glucuronide, a quinazolinone, a quinazoline carboxylic acid, and two hydroxylorazepam isomers, one of which is novel, having the hydroxyl group located on the fused chlorobenzene ring. The quinazolinone, and particularly the quinazoline carboxylic acid metabolite, provided longer detection windows than lorazepam in urine extracts not subjected to enzymatic hydrolysis, a finding that is highly relevant to toxicology laboratories that omit hydrolysis in order to rapidly reduce the time spent on gas chromatography-mass spectrometry (GC-MS) analysis. With hydrolysis, the longest windows of detection were achieved by monitoring lorazepam, supporting the targeting of the aglycone with free drug for those incorporating hydrolysis in their analytical toxicology procedures.

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Section: Discussionmentioning

confidence: 99%

Metabolites of lorazepam: Relevance of past findings to present day use of LC‐MS/MS in analytical toxicology

Turfus¹,

Braithwaite²,

Cowan³

et al. 2011

Drug Testing and Analysis

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show abstract

“…Herman et al [10] reported that lorazepam cannot properly be used as a marker of conjugative metabolism due to the fact that it undergoes significant enterohepatic recirculation in humans. Herman et al [19] associated neomycin and cholestyramine in an attempt to block the enterohepatic circulation of lorazepam and to permit an in vivo estimate of hepatic glucuronidation.…”

Section: Introductionmentioning

confidence: 99%

Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples

Papini

Cunha

Mathes

et al. 2006

Journal of Pharmaceutical and Biomedical Analysis

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Human Versus Porcine Insulin in Patients with Insulin-dependent Diabetes Mellitus: Differences in Sleep and the Sleep EEG During Near-normoglycemia

Roth

Landolt²,

Achermann³

et al. 1998

Sleep

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To investigate whether porcine insulin (PI) and human insulin (HI) have different effects on brain functions outside of hypoglycemia, sleep and the sleep EEG were recorded in eight insulin-dependent diabetes mellitus (IDDM) patients in three separate sessions of 2 consecutive nights. Near-normoglycemia was confirmed by measurements of capillary blood glucose before and after sleep and at 0145 hours. The treatment effect (PI compared to HI) consisted of a change in the NREM sleep EEG in the spindle frequency range. Spectral power density in the 14-Hz bin was reduced upon transfer from PI (session 1) to HI (session 2) in all subjects, and increased upon reversal to PI (session 3) in all but one subject. There were no significant treatment effects on any other sleep EEG variable or on sleep stages. The subjects rated their sleep as more sound and their state in the morning as more relaxed during PI treatment. They were, however, not blinded to the type of insulin they were using. Porcine insulin and human insulin may exert differential effects on spindle-generating mechanisms in the thalamocortical system. The results indicate that human insulin may affect brain functions differently compared to animal insulin under near-normoglycemic conditions.

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Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins

Cited by 3 publications

References 32 publications

Metabolites of lorazepam: Relevance of past findings to present day use of LC‐MS/MS in analytical toxicology

Metabolites of lorazepam: Relevance of past findings to present day use of LC‐MS/MS in analytical toxicology

Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples

Human Versus Porcine Insulin in Patients with Insulin-dependent Diabetes Mellitus: Differences in Sleep and the Sleep EEG During Near-normoglycemia

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