The Obesogenic Potency of Various High-Caloric Diet Compositions in Male Rats, and Their Effects on Expression of Liver and Kidney Proteins Involved in Drug Elimination

Abdussalam, Ali; Elshenawy, Osama H.; Jardan, Yousef A. Bin; El‐Kadi, Ayman O.S.; Brocks, Dion R.

doi:10.1016/j.xphs.2017.02.002

Cited by 13 publications

(6 citation statements)

References 50 publications

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“…Two significant relationships were observed (Figure ), BMI vs t ½ (positive) and age vs CL/ F (negative). In rats, decreases in hepatic blood flow occur with higher age and body weight, as are levels and activities of hepatic cytochrome P450 3A isoforms (involved in lidocaine metabolism) . Hepatic and portal blood flow has been shown to decrease with general anaesthesia, particularly in older patients (>55 years), and mean age of our patients was 63.9 years.…”

Section: Discussionmentioning

confidence: 72%

“…In rats, decreases in hepatic blood flow occur with higher age and body weight, as are levels and activities of hepatic cytochrome P450 3A isoforms (involved in lidocaine metabolism). [32][33][34] Hepatic and portal blood flow has been shown to decrease with general The optimal pharmacokinetic (PK) model as one (1c) or two (2c) are indicated for each patient.…”

Section: Discussionmentioning

confidence: 99%

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Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations

Primrose

Nebaihi

Brocks

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Rectus sheath blocks are an established option for analgesia following abdominal surgery, but pharmacokinetic data are limited. This study sought to characterise the absorption of lidocaine injectate and the pharmacokinetics of lidocaine after rectus sheath injection. Methods Bilateral rectus sheath single‐injection blocks were given to 10 patients undergoing general or urological surgery. Afterwards, serial lidocaine serum levels and ultrasound measurements of the rectus sheath injectate reservoir were collected. Key findings Injectate within the rectus sheath was visible with ultrasound up to 12 h after injection. However, the rate of drug absorption exceeded that of injectate disappearance. Peak serum concentration occurred within 30 min with average peak concentrations of 1.65 μg/ml. Lidocaine clearance was lower than reported in young healthy subjects. The body mass index positively correlated with lidocaine terminal phase half‐life, and clearance negatively correlated with age. Conclusions The study provides the first data describing lidocaine pharmacokinetics after rectus sheath injection. Peak serum concentrations transiently achieved systemic levels associated with pain relief after a single bolus injection. The data from this study could be used to develop a regime using single shot rectus sheath blockade with a bolus of lidocaine followed by infusion using bilateral rectus sheath catheters.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations

Primrose

Nebaihi

Brocks

et al. 2019

Journal of Pharmacy and Pharmacology

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“… 87 Fukuchi et al 88 provided evidence that amiodarone clearance was affected by BMI, reduced by 22.3% when BMI was >25 kg/m 2 , thus resulting in significantly higher serum concentration in obese patients. Reduced expression of cytochrome P450 enzymes in HFD mice was demonstrated, 89 providing a likely mechanism for reduced elimination of amiodarone. Reduced hepatic metabolism and increased levels of amiodarone‐binding proteins may contribute to altered amiodarone pharmacokinetics in obesity.…”

Section: The Effect Of Obesity On Rhythm Controlmentioning

confidence: 97%

“…Reduced hepatic metabolism and increased levels of amiodarone‐binding proteins may contribute to altered amiodarone pharmacokinetics in obesity. 89 …”

Section: The Effect Of Obesity On Rhythm Controlmentioning

confidence: 99%

Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options

Sha,

Baines,

Hayes

et al. 2024

JAHA

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Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like hypertension, diabetes, and heart failure. Obesity‐driven structural and electrical remodeling contribute to AF via several reported mechanisms, including adiposity, inflammation, fibrosis, oxidative stress, ion channel alterations, and autonomic dysfunction. In particular, expanding epicardial adipose tissue during obesity has been suggested as a key driver of AF via paracrine signaling and direct infiltration. Weight loss has been shown to reverse these changes and reduce AF risk and recurrence after ablation. However, studies on how obesity affects pharmacologic or interventional AF treatments are limited. In this review, we discuss mechanisms by which obesity mediates AF and treatment outcomes, aiming to provide insight into obesity‐drug interactions and guide personalized treatment for this patient subgroup.

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“…A number of investigations have been performed in rodents (mice, rats, and guinea pigs) to examine the effects of overweight/obesity on drug metabolizing enzymes. In Table 2, a summary of the data is shown from studies measuring protein concentration by immunoblot techniques or by activity using specific chemical probes (83,85,87,89,96,97,99,100,104,105,108,116,(118)(119)(120)(121)(122)(123)(124)(125)(126)(127)(128). Because mRNA is not the final determinant of the protein present, and because changes in mRNA do not always follow those of translation to protein or enzyme activity, those data are not included in this review.…”

Section: Studies Involving Rodentsmentioning

confidence: 99%

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

et al. 2022

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In many comparative trials examining the effects of adult obesity on pharmacokinetics of drugs, conclusions were made based on values that were either not adjusted to total body weight or adjusted to non-obese body mass (e.g., ideal or lean body weight). In many cases these values were higher in the obese subjects. We have reviewed the data from comparative human trials, and it is apparent that in examining clearance normalization to total body weight (as typically done in studies involving pediatric obese patients), the clearances are often reduced in the obese. We have also reviewed the results of experimental obese versus non-obese rodent models. Those studies have mostly found that the systemic exposures to the same dose per body weight are increased, with obesity-related decreases in clearance. Furthermore, the expression of a number of important drug metabolizing enzymes are reduced in the experimental obese state. There is also evidence that obesity causes increases in the measured mass of eliminating organs such as liver and kidney. Human clearance normalized to total body weight appears to better reflect the underlying changes reported in the expression of protein and functional activity of drug clearance mechanisms.

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The Obesogenic Potency of Various High-Caloric Diet Compositions in Male Rats, and Their Effects on Expression of Liver and Kidney Proteins Involved in Drug Elimination

Cited by 13 publications

References 50 publications

Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations

Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations

Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

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