Clinical Pharmacokinetics of Metoprolol: A Systematic Review

Zamir, Ammara; Hussain, Iltaf; Rehman, Anees Ur; Ashraf, Waseem; Imran, Imran; Saeed, Hamid; Majeed, Abdul; Alqahtani, Faleh; Rasool, Muhammad Fawad

doi:10.1007/s40262-022-01145-y

Cited by 15 publications

(16 citation statements)

References 58 publications

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“…18 Various pathophysiological changes appear in CKD that can modify the metoprolol PK and may intensify its relevant side effects. 11 The changes in albumin, hematocrit, small intestinal transit time, and gastric emptying time are reported in the previously published literature, 19,20 and upon integrating them into the PK model, it may help in optimizing the doses of metoprolol among CKD patients. PBPK models on metoprolol have already been developed in the past, among which few put the emphasis on polymorphism, i.e., influence of different genotypes of CYP2D6 on its distribution and elimination, 21−23 some were focused on a special population (pregnant), 24−26 whereas others were concentrated on predicting PK of metoprolol following different routes of administration (IV, PO, immediate, and controlled-release).…”

Section: Introductionmentioning

confidence: 96%

“…Metoprolol being a cardio-selective β-1 blocker drug is indicated in the cure of hypertension and various cardiovascular illnesses with formulations available in intravenous (IV), per-oral (PO), immediate-release, extended-release, controlled-release, and slow-release . This drug is devoid of its intrinsic sympathomimetic activity.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic kidney disease (CKD) is characterized by irregularities in the kidney structure or function and a reduction in estimated glomerular filtration rate (eGFR) to <60 mL/min . Various pathophysiological changes appear in CKD that can modify the metoprolol PK and may intensify its relevant side effects . The changes in albumin, hematocrit, small intestinal transit time, and gastric emptying time are reported in the previously published literature, , and upon integrating them into the PK model, it may help in optimizing the doses of metoprolol among CKD patients.…”

Section: Introductionmentioning

confidence: 99%

“…2,6−10 Metoprolol being a cardio-selective β-1 blocker drug is indicated in the cure of hypertension and various cardiovascular illnesses with formulations available in intravenous (IV), per-oral (PO), immediate-release, extended-release, controlledrelease, and slow-release. 11 This drug is devoid of its intrinsic sympathomimetic activity. In the heart and blood vessels, β-1 receptors are present which are competitively inhibited by metoprolol, giving rise to a decrease in the heart rate, the oxygen demand of cardiac muscles, and cardiac output, thus reducing the effects of hypertension and angina.…”

Section: Introductionmentioning

confidence: 99%

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Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations

et al. 2023

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The evolution in the development of drugs has increased the popularity of physiologically based pharmacokinetic (PBPK) models. This study seeks to assess the PK of metoprolol in populations with healthy, chronic kidney disease (CKD), and acute myocardial infarction (AMI) conditions by developing and evaluating PBPK models. An extensive literature review for identifying and selecting plasma concentration vs time profile data and other drug-related parameters was undergone for their integration into the PK-Sim program followed by the development of intravenous, oral, and diseased models. The developed PBPK model of metoprolol was then evaluated using the visual predictive checks, mean observed/predicted ratios (R obs/pre), and average fold error for all PK parameters, i.e., the area under the curve (AUC), maximal plasma concentration, and clearance. The model evaluation depicted that none of the PK parameters were out of the allowed range (2-fold error) in the case of the mean R obs/pre ratios. The model anticipations were executed to determine the influence of diseases on unbound and total AUC after the application of metoprolol in healthy, moderate, and severe CKD. The dosage reductions were also suggested based on differences in unbound and total AUC in different stages of CKD. The developed PBPK models have successfully elaborated the PK changes of metoprolol occurring in healthy individuals and those with renal and heart diseases (CKD & AMI), which may be fruitful for dose optimization among diseased patients.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations

et al. 2023

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“…Metoprolol is a β‐adrenergic receptor blocker commonly prescribed for the treatment of acute anxiety‐related disorders, hypertension, and cardiovascular diseases 1–3 . Metoprolol is ranked among the top 20 frequently prescribed drugs in the United States and its consumption has been snowballing yearly across the globe 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs

Oyedele

Adedara

Ikeji

et al. 2023

Environmental Toxicology

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Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 μg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video‐tracking software (ANY‐maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol‐exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol‐mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol‐exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido‐inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.

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Impact of amiodarone use on metoprolol concentrations, α‐OH‐metoprolol concentrations, metoprolol dosing and heart rate: A cross‐sectional study

Robert,

Pilon,

Oussaïd

et al. 2023

Pharmacology Res & Perspec

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Small studies suggest that amiodarone is a weak inhibitor of cytochrome P450 (CYP) 2D6. Inhibition of CYP2D6 leads to increases in concentrations of drugs metabolized by the enzyme, such as metoprolol. Considering that both metoprolol and amiodarone have β‐adrenergic blocking properties and that the modest interaction between the two drugs would result in increased metoprolol concentrations, this could lead to a higher risk of bradycardia and atrioventricular block. The primary objective of this study was to evaluate whether metoprolol plasma concentrations collected at random timepoints from patients enrolled in the Montreal Heart Institute Hospital Cohort could be useful in identifying the modest pharmacokinetic interaction between amiodarone and metoprolol. We performed an analysis of a cross‐sectional study, conducted as part of the Montreal Heart Institute Hospital Cohort. All participants were self‐described “White” adults with metoprolol being a part of their daily pharmacotherapy regimen. Of the 999 patients being treated with metoprolol, 36 were also taking amiodarone. Amiodarone use was associated with higher metoprolol concentrations following adjustment for different covariates (p = .0132). Consistently, the association between amiodarone use and lower heart rate was apparent and significant after adjustment for all covariates under study (p = .0001). Our results highlight that single randomly collected blood samples can be leveraged to detect modest pharmacokinetic interactions.

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Clinical Pharmacokinetics of Metoprolol: A Systematic Review

Cited by 15 publications

References 58 publications

Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations

Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations

Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs

Impact of amiodarone use on metoprolol concentrations, α‐OH‐metoprolol concentrations, metoprolol dosing and heart rate: A cross‐sectional study

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