Species Differences in the Pharmacokinetic Parameters of Cytochrome P450 Probe Substrates between Experimental Animals, such as Mice, Rats, Dogs, Monkeys, and Microminipigs, and Humans

S, Sakai C Iwano

doi:10.4172/2157-7609.1000173

Cited by 14 publications

(6 citation statements)

References 54 publications

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“…From the graph, it can be seen that the peak caffeine level in the blood was achieved at 30 minutes after oral administration and the maximum concentration of caffeine in the sample blood was 0.582 ± 0.249 μg/ml (Figure 2). This is consistent with the study conducted by Iwano (2015) . Caffeine is rapidly absorbed after oral administration and the peak level in blood is usually reached within 30 minutes (Roy & Das, 2015).…”

Section: Extraction Fractionation and Isolationsupporting

confidence: 93%

Determination Levels of Caffeine Isolated from Robusta Coffee Beans from Pagar Alam in Wistar Rat Blood

et al. 2022

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Coffee provides a genuine source of caffeine. Caffeine can have a variety of pharmacological effects on both central and peripheral nervous systems and most of these effects are related to the antagonistic mechanism at adenosine receptors. The most prominent effect of caffeine remains stimulation of brain function, improving mood and physical performance. Robusta coffee obtains an intense level of caffeine and Pagar Alam City is one of the cities in Indonesia that produces robusta coffees. This study aims to identify and characterize caffeine isolated from Pagar Alam robusta coffee beans using thin-layer chromatography methods, UV-Visible spectrophotometry and to determine caffeine levels in wistar rat blood using the ELISA method. This method is cost-effective, familiar to perform and has a considerable degree of accuracy and reproducibility. The isolated samples have similar characteristics to standard caffeine with an Rf value of 0.77, a maximum wavelength at 273 nm with the absorbance of 1.3 and from caffeine profile in the blood sample we obtained the maximum sample concentration in blood 0.582 ± 0.249 μg/ml and the time needed to reach the maximum concentration is 30 minutes.

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Section: Extraction Fractionation and Isolationsupporting

confidence: 93%

Determination Levels of Caffeine Isolated from Robusta Coffee Beans from Pagar Alam in Wistar Rat Blood

et al. 2022

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“…It is to be stated that the CYP450 isoforms in humans and dogs are not strictly identical, neither by their protein sequence, nor by their affinities for substrates. The human and canine genes are not clear orthologues (Bogaards et al 2000;Shou et al 2003;Martignoni et al 2006;Turpeinen et al 2007;Court 2013;Martinez et al 2013;Sakai et al 2014), and they also differ by their genetic polymorphisms (Martinez et al 2013;van Hagen et al 2020;Karakus et al 2021). Similarly, selective inhibitors of human P450 isoforms may not display similar selective properties in dog microsomes (Martinez et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Citalopram in vitro metabolism in a beagle dog: A role for CYP2D15 in the production of toxic didesmethylcitalopram?

Rochat¹,

Paus²,

Maître³

et al. 2023

Vet. Med.

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After administration of the serotonergic antidepressant citalopram (CIT) to Beagle dogs, the dogs may experience severe convulsive attacks in relation to the considerably higher plasma concentrations of the metabolite didesmethyl-CIT (DDCIT), when compared to those in humans medicated with CIT. This pilot study aimed at determining the role of cytochrome P-450 (CYP450) isozymes in the in vitro metabolism of CIT to desmethyl-CIT (DCIT), and of DCIT to DDCIT in the liver microsomes of a single Beagle dog. Incubations with racemic CIT or DCIT reveal a high-affinity enzyme with K m between 0.3 µM and 1.4 µM for S-and R-DCIT and S-and R-DDCIT productions, respectively. In comparison to human enzymes, the intrinsic clearance values of this highaffinity enzyme are between 15 µl/(min × mg of protein) and 52 µl/(min × mg of protein), i.e., very high. In vitro experiments with inhibitors suggest that CYP2D15, which shows an analogy with human CYP2D6, is by far the main CYP450 isozyme involved in the production of DCIT and DDCIT, whereas CYP3A12 and CYP2C21/41 showed a weak implication. These observations partly explain why, in humans, the plasma concentrations of the toxic DDCIT are considerably lower than those observed in dogs, after administration of CIT.

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“…Исследования in vivo. Модели гепатотоксичности на лабораторных животных не всегда релевантны даже при исследовании прямой ЛГТ вследствие межвидовых различий [31]. Тем не менее есть несколько моделей, позволяющих исследовать механизмы иЛГТ.…”

Section: доклинические исследованияunclassified

“…Metushi и соавт. [31] у мышей с нокаутированным геном PD-1 препарат амодиахинин вызывал более тяжелое повреждение печени, чем у мышей дикого типа, у которых нарушения функции печени проходили самопроизвольно. Дополнительное подавление антителами цитотоксического CTLA-4, который играет одну из ведущих ролей в иммунотолерантности, приводило к развитию более тяжелых повреждений печени, сходных с иЛГТ у человека.…”

Section: доклинические исследованияunclassified

Idiosyncratic Drug-Induced Liver Injury: From Pathogenesis to Risk Reduction

Мазеркина¹

2023

Bezopasnost' i risk farmakoterapii

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Idiosyncratic drug-induced liver injury (iDILI) is a rare and poorly predictable adverse drug reaction that may lead to death or liver transplantation in severe cases.The aim of the study was to review contemporary concepts of the immune-mediated pathogenesis of iDILI and possible ways to predict and prevent the risk of developing this condition.The liver is characterised by high immune tolerance due to a complex of mechanisms involving various cells (antigen-presenting cells, T-cells), cytokines, and other molecules, which prevents severe immune responses to xenobiotics entering the body. Previous research has shown that iDILI results from a combination of multiple synergistic unfavourable factors that impair liver immune tolerance at different levels. These factors include the hepatotoxicity-associated chemical properties of medicines and the individual characteristics of the patient, including the genetically determined structure and function of the adaptive immune system components. Since iDILI has a multilevel and multifactor pathogenesis, it is difficult to determine a risk biomarker for a particular medicine. According to the literature review, the risk of hepatotoxicity of a drug candidate and/or a metabolite can be reduced at the preclinical level by assessing the ability to cause mitochondrial damage, form non-covalent bonds, produce reactive oxygen species, and release damage-associated molecular patterns (DAMPs). The association of iDILI with gene polymorphisms in patients receiving certain medicines has a high negative predictive value and can be used in clinical practice to rule out iDILI or identify hepatotoxic medicinal products in polypharmacy. The identification of the allele combinations associated with an increased risk of iDILI seems promising for enhancing the predictive value of genetic studies and may be used in personalised medicine.

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Species Differences in the Pharmacokinetic Parameters of Cytochrome P450 Probe Substrates between Experimental Animals, such as Mice, Rats, Dogs, Monkeys, and Microminipigs, and Humans

Cited by 14 publications

References 54 publications

Determination Levels of Caffeine Isolated from Robusta Coffee Beans from Pagar Alam in Wistar Rat Blood

Determination Levels of Caffeine Isolated from Robusta Coffee Beans from Pagar Alam in Wistar Rat Blood

Citalopram in vitro metabolism in a beagle dog: A role for CYP2D15 in the production of toxic didesmethylcitalopram?

Idiosyncratic Drug-Induced Liver Injury: From Pathogenesis to Risk Reduction

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