Metoprolol tartrate pharmacokinetics
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Metoprolol Tartrate Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion
Oral Pharmacokinetics in Healthy Volunteers
Metoprolol tartrate, when administered orally, is rapidly absorbed with a typical time to reach maximum plasma concentration (Tmax) of about 1 to 1.7 hours and a maximum concentration (Cmax) ranging from approximately 63 to 186 ng/mL, depending on the dose and population studied 13. The area under the plasma concentration-time curve (AUC), which reflects overall drug exposure, varies but is generally around 400–860 ng·h/mL for a single 50–100 mg dose in healthy adults 13. Multiple dosing increases AUC and Cmax, indicating some accumulation with repeated administration 1.
Controlled-Release and Alternative Formulations
Controlled-release formulations of metoprolol tartrate show a lower Cmax and a delayed Tmax (up to 8 hours), with a more prolonged mean residence time (MRT) compared to immediate-release tablets, indicating a sustained-release effect 2. Rectal suppository formulations in animal models have demonstrated higher AUCs and faster pharmacological effects compared to oral tablets, likely due to avoidance of first-pass metabolism 6.
Intravenous and Oral Pharmacokinetics in Animals
In animal studies, such as those conducted in horses, oral bioavailability of metoprolol tartrate is about 54%, with a Cmax of 2135 ng/mL reached at 0.5 hours post-administration. The elimination half-life is short, around 21 minutes, and the drug is rapidly cleared from the system 4.
Impact of CYP2D6 Genetic Polymorphism
Metoprolol is primarily metabolized by the CYP2D6 enzyme. Genetic differences in CYP2D6 significantly affect metoprolol pharmacokinetics. Individuals with reduced CYP2D6 function (e.g., *10 or *5 alleles) have much higher AUCs, indicating slower metabolism and greater drug exposure. For example, AUCinf can range from about 493 ng·h/mL in wild-type genotypes to over 5000 ng·h/mL in poor metabolizers 5. Physiologically based pharmacokinetic (PBPK) models can predict these differences and help guide individualized dosing 5.
Age, Disease, and Drug Interactions
Age has a modest effect on metoprolol pharmacokinetics. Elderly individuals may have higher concentrations of certain active metabolites, but overall metoprolol levels are similar to those in younger adults 7. In patients with hepatic impairment, clearance is reduced, leading to higher drug exposure, while renal impairment may increase clearance 8. Co-administration with other drugs or substances, such as quercetin, can significantly reduce metoprolol plasma levels, highlighting the importance of monitoring for drug interactions 810.
Effects of Gastric Bypass Surgery
After Roux-en-Y gastric bypass surgery, the oral exposure (AUC) of metoprolol may increase by 32–56%, possibly due to reduced first-pass metabolism and weight loss, but these changes are not always statistically significant 9.
Conclusion
Metoprolol tartrate pharmacokinetics are influenced by formulation type, genetic factors (especially CYP2D6 polymorphism), age, disease states, and drug interactions. Immediate-release forms are rapidly absorbed, while controlled-release and rectal formulations alter absorption profiles and overall exposure. Individualized dosing may be necessary for patients with genetic differences in metabolism, liver disease, or those taking interacting medications. Understanding these pharmacokinetic properties is essential for optimizing metoprolol therapy and minimizing adverse effects.
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