A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model

Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi‐Khansari, Mahmoud

doi:10.1016/j.biopha.2017.04.082

Cited by 7 publications

(8 citation statements)

References 16 publications

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“…Bile duct ligation (BDL) surgery was used to induce hepatic dysfunction in a preclinical rat model. The BDL surgery rapidly produces hepatic fibrosis (19) and is known to impair the clearance of hepatically eliminated drugs (20)(21)(22). In control animals, a sham surgery was performed which involved bile duct isolation without ligation.…”

Section: Introductionmentioning

confidence: 99%

Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

et al. 2019

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Purpose: Methamphetamine (METH) abuse is associated with hepatic dysfunction related comorbidities such as HIV, hepatitis C, and polysubstance abuse with acetaminophen-containing opioid formulations. We aimed to develop a bile duct ligation (BDL)-induced hepatic dysfunction model for studying both METH and experimental treatments for METH abuse in this comorbidity. Methods: Sham or BDL surgery was performed in male Wistar rats on day 0. Liver function was measured throughout the study. On days 7 and 19, serum pharmacokinetics studies were performed with 1 mg/kg subcutaneous (sc) METH. On day 21, this dose was repeated to determine 2 h post-METH brain concentrations. METH-induced open field behaviors were measured every other day (days 12 -16) with ascending sc doses (0.3 -3 mg/kg). Results: BDL transiently increased alanine aminotransferase levels and altered liver structure, which resulted in significantly greater METH serum and brain exposure. In the BDL compared to sham group, there was a longer duration of METH-induced locomotor activity (after 1 and 3 mg/kg) and stereotypy (after 3 mg/kg). Conclusions: In rats, liver dysfunction reduced METH clearance, increased brain METH concentrations, and enhanced METH effects on locomotor activity in a dose dependent manner. In addition, this model could be further developed to simulate the associated hepatic dysfunction of key METH abuse comorbidities for preclinical testing of novel pharmacotherapies for effectiveness and/or toxicity in vulnerable populations.

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Section: Introductionmentioning

confidence: 99%

Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

et al. 2019

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“…However, treatment with naloxone reverses the analgesic effect produced via cholestasis and opioid drugs. We proposed that alone administration of morphine or tramadol, as well as co-administration of them, together resulted in the activation of µ-opioid receptors as well as activation of catecholamine and serotonergic receptors (Gholami et al, 2015, Esmaeili et al, 2017, Subedi et al, 2019 which caused an analgesic effect in cholestatic and addicted mice. This is in agreement with other studies that the administration of morphine and tramadol produced an anti-nociceptive effect through the activation of µ-opioid receptors (Fazli-Tabaei et al, 2005, Zeng et al, 2013, Sousa and Ashmawi, 2015).…”

Section: Effects Of Cholestasis and Drug Dependence On Pain Behaviorsmentioning

confidence: 99%

“…Tramadol is described as safe since it does not prompt addiction when compared with other opioid analgesics (Preston et al, 1991, Subedi et al, 2019. It prompts an analgesia property by presenting the agonistic activity to the µ-opioid receptors as well as catecholamine and serotonergic receptors (Gholami et al, 2015, Esmaeili et al, 2017, Subedi et al, 2019. Moreover, the combination of a μ-opioid agonist with another non-μ-opioid analgesic may have augmented analgesic effectiveness and/or a better safety pro le (Smith, 2008).…”

Section: Effects Of Cholestasis and Drug Dependence On Pain Behaviorsmentioning

confidence: 99%

“…Surgical processes of acute liver injury and repair, such as partial hepatectomy or bile duct ligation (BDL), have been done for decades in rodents to investigate liver regeneration and pathophysiology. The most commonly used experimental technique for the production of cholestasis is BDL (Zhang et al, 2012, Esmaeili et al, 2017). In BDL, the common bile duct is ligated that induces functional and structural variations (Baumgartner et al, 1995) in the liver parenchyma via the intrahepatic and systemic accumulation of the bile salts which causes progressive brogenesis, in ammation, and cirrhosis (Heinrich et al, 2011, Zarrindast et al, 2012, Yokota et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Anxiolytic and Analgesic Effectiveness and/or a Better Safety Profile of Morphine and Tramadol Combination in Cholestatic and Addicted Mice

Khakpai

Issazadeh

Rezaei

2022

Preprint

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The involvement of the opioidergic system on anxiolytic and anti-nociceptive responses induced by cholestasis was investigated in cholestatic and addicted mice. Elevated plus-maze and tail-flick devices were used to assess anxiety and pain levels, respectively. The data indicated that induction of cholestasis and injection of opioid drugs including morphine and tramadol enhanced %OAT and %OAE but naloxone reduced %OAT and %OAE in the sham-operated and bile duct ligated (BDL) mice. Induction of cholestasis and addiction to morphine and tramadol prolonged tail-flick latency which was reversed by naloxone. Co-administration of morphine and tramadol enhanced anxiolytic and analgesic effects in the sham-operated and BDL mice. It seems (i) cholestasis and addiction affect anxiety and pain behaviors, (ii) µ-opioid receptors play a key role in anxiolytic and analgesic effects induced by cholestasis, (iii) co-treatment with morphine and tramadol augmented the effectiveness of them for induction of anxiolytic and analgesic effects both in cholestatic and addicted mice.

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“…As a synthetic opioid, tramadol has been widely used for its pain-relieving effects 1 – 4 . It was originally manufactured in Germany in 1977 5 , 6 and then in other countries some 20 years later. Tramadol, a pharmaceutical opioid, has been used as a painkiller for decades, but its non-medical use has caused a crisis of synthetic opioid overdoses in many subregions, in particular West, Central and North Africa, which requires urgent international attention 7 .…”

Section: Introductionmentioning

confidence: 99%

A comparative study of postmortem distribution and postmortem diffusion of tramadol in rabbits

Wang

Wurita

et al. 2023

Sci Rep

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In recent years, the cases of tramadol intoxication have become more frequent in many countries. However, most of the previous studies have been based on cases of tramadol intoxication, and the detailed information on the differences between postmortem distribution and diffusion of tramadol remains unclear. To investigate this issue systematically, we established a postmortem distribution model and two postmortem diffusion models. Then, gas chromatography-mass spectrometry (GC/MS) was used to measure the concentrations of tramadol in various biological specimens of fluids and tissues. In postmortem distribution, the results showed an uneven distribution of tramadol in various biological specimens, and the concentrations of tramadol in urine were significantly higher than those in other fluids. In postmortem diffusion, the results showed a dosage-dependent increase of tramadol concentration in most specimens; at all time points from 0.25 to 6 h after postmortem administration, the concentrations of tramadol in fluids were not significantly different from those in tissues, and the concentrations of tramadol in urine were lower than those in both tissues and other fluids in most time points. We recommend a quantitative examination of the specimens of both fluids and tissues to provide more evidence for the forensic identification, and the realization that there is a correlation between the concentrations of fluids and tissues is important for determining antemortem and postmortem administration of tramadol. This information can serve as ancillary data in inferring the contribution of a drug to death in cases of suspected tramadol poisoning.

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A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model

Cited by 7 publications

References 16 publications

Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

Effect of Bile Duct Ligation-induced Liver Dysfunction on Methamphetamine Pharmacokinetics and Locomotor Activity in Rats

Enhanced Anxiolytic and Analgesic Effectiveness and/or a Better Safety Profile of Morphine and Tramadol Combination in Cholestatic and Addicted Mice

A comparative study of postmortem distribution and postmortem diffusion of tramadol in rabbits

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