Metoprolol controlled substance
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Metoprolol Controlled Substance: Pharmacokinetics and Pharmacodynamics
Introduction to Metoprolol Controlled Release (CR) Formulations
Metoprolol, a β1-selective adrenoceptor blocking agent, is widely used for treating hypertension, angina pectoris, and for secondary prevention following myocardial infarction. The development of controlled-release (CR) formulations of metoprolol aims to provide a more consistent therapeutic effect by maintaining steady plasma concentrations over an extended period.
Pharmacokinetic Properties of Metoprolol CR
Steady State Pharmacokinetics
Studies comparing metoprolol CR/ZOK (controlled release, zero order kinetics) with conventional metoprolol tablets and atenolol have shown that the CR formulation provides more stable plasma concentrations. In a study involving healthy Oriental men, metoprolol CR/ZOK demonstrated less variability in plasma levels compared to conventional metoprolol tablets, which exhibited significant peaks and troughs1. This stability is crucial for maintaining consistent therapeutic effects and minimizing side effects.
Continuous Delivery and Absorption
The CR formulation of metoprolol is designed to release the drug continuously over 24 hours. This is achieved through a tablet consisting of multiple coated pellets, each acting as an individual controlled-release unit. This design ensures that the drug's release is independent of physiological variables such as pH and food intake, leading to smooth plasma concentration profiles without significant fluctuations3.
Pharmacodynamic Properties of Metoprolol CR
Efficacy and Tolerability
Metoprolol CR/ZOK has been shown to provide effective and well-tolerated treatment for hypertension and angina pectoris. The continuous, even plasma concentrations achieved with the CR formulation ensure a consistent therapeutic effect, which is particularly beneficial for patients requiring long-term management of cardiovascular conditions2.
Combination with Hydrochlorothiazide
When combined with hydrochlorothiazide, a diuretic, the controlled-release formulation of metoprolol maintains effective β1-adrenoceptor blockade for 24 hours without affecting the pharmacokinetics of hydrochlorothiazide. This combination has been shown to produce a greater total effect on exercise heart rate compared to conventional formulations, despite a lower relative systemic availability of metoprolol from the CR formulation4.
Conclusion
The development of controlled-release formulations of metoprolol represents a significant advancement in the management of cardiovascular diseases. By providing stable plasma concentrations and consistent therapeutic effects, metoprolol CR formulations improve patient outcomes and adherence to treatment regimens. The combination of metoprolol CR with other agents like hydrochlorothiazide further enhances its therapeutic potential, making it a valuable option in the treatment of hypertension and related conditions.
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Most relevant research papers on this topic
Pharmacokinetic and Pharmacodynamic Properties of Controlled Release (CR/ZOK) Metoprolol in Healthy Oriental Subjects: A Comparison with Conventional Formulations of Metoprolol and Atenolol
Controlled release metoprolol (CR/ZOK) shows better pharmacokinetic and pharmacodynamic properties compared to conventional metoprolol and atenolol in healthy Oriental men.
RCTMETOPROLOL—CONTROLLED RELEASE, ZERO ORDER KINETICS
Metoprolol CR/ZOK is a new formulation of a well-tolerated beta-blocker for treating hypertension, angina pectoris, and secondary prevention after a myocardial infarct.
Design of a new multiple-unit controlled-release formulation of metoprolol — Metoprolol CR
The new controlled-release formulation of metoprolol CR provides smooth 24-hour pharmacological effects, independent of pH and physiological variables, without peaks or troughs.
The pharmacokinetics and pharmacodynamics of metoprolol after conventional and controlled-release administration in combination with hydrochlorothiazide in healthy volunteers
Controlled-release metoprolol with hydrochlorothiazide provides effective 1-adrenoceptor blockade for 24 hours without affecting hydrochlorothiazide's pharmacokinetics.
Non-RCTPharmacokinetics and pharmacodynamics of controlled-release metoprolol: A comparison with atenolol
The controlled-release metoprolol formulation has more even reduction in exercise heart rate and systolic blood pressure compared to atenolol, with less fatigue during exercise at peak plasma concentrations.
RCTPharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: A comparison with conventional tablets
The new controlled-release metoprolol formulation maintains a constant degree of 1-selective blockade without plasma peaks and troughs, offering potential benefits over conventional tablets.
Non-RCT
Highly CitedControlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease.
Controlled release metoprolol formulations (metoprolol CR/ZOK and metoprolol OROS) effectively reduce blood pressure and treat ischemic heart disease, with potential benefits for asthmatics and healthy individuals.
Literature ReviewDevelopment of A New Controlled Release Metoprolol Product
A new controlled-release metoprolol product has been developed for once-daily dosage, providing a pH-independent and constant release over 20 hours, with good manufacturing reproducibility and uniform plasma concentration-time curves in vivo.
Controlled Release Metoprolol Formulations
Controlled release metoprolol formulations (metoprolol CR/ZOK and metoprolol OROS) provide effective blood pressure reduction and 1-blockade while maintaining convenience and safety in once daily administration for patients with hypertension and stable angina pectoris.
Non-RCTEffect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF)
Metoprolol CR/XL once daily in addition to standard therapy improved survival in chronic heart failure patients with decreased ejection fraction and symptoms, and was well-tolerated.
RCT
Large Human TrialHighly Cited