Metoprolol in Acute Myocardial Infarction. A PK/PD Study

Study Overview
=================
Brief Summary
-----------------
The objective of the study was to compare treatment with two different oral formulations of metoprolol, metoprolol immediate release (IR) and metoprolol extended release (CR/XL) in patients with acute myocardial infarction regarding the following: Pharmacokinetics, peak and trough plasma concentrations and area under the plasma concentration curve. Pharmacodynamics, hourly means of Holter recorded heart rate. Tolerability. An open, randomised design with two parallel groups was employed.

Detailed Description
-----------------
A pharmacokinetic and pharmacodynamic study comparing metoprolol IR and metoprolol CR/XL subsequent to initial treatment with intravenous and/or oral metoprolol in patients with suspected acut myocardial infarction

Official Title
-----------------
A Pharmacokinetic and Pharmacodynamic Study Comparing Metoprolol IR and Metoprolol CR/XL Subsequent to Initial Treatment With Intravenous and/or Oral Metoprolol in Patients With Suspected Acut Myocardial Infarction

Conditions
-----------------
Acute Myocardial Infarction

Intervention / Treatment
-----------------
* Drug: Metoprolol- Toprol XL
* Drug: Metoprolol- Lopressor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients admitted to the CCU with suspected acute myocardial infarction Age 18 years or older Treated with and tolerated the full dose of metoprolol IR 50 mr four times daily or metoprolol CR/XL 200 mg once daily on study day 1 Expected to stay in the CCU until the morning of study day 4 Sinus rhythm on the day of admission and at randomisation Exclusion Criteria: Pregnancy or childbearing potential without adequate contraception Participation in a clinical study during the last 30 days or previous randomisation in the present study
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metoprolol- Toprol XL<br>Metoprolol extended release (CR/XL) tablet 200 mg once daily | Drug: Metoprolol- Toprol XL<br>* Extended release tablet, 200mg once daily for 4 days<br>|
| Active Comparator: Metoprolol- Lopressor<br>Metoprolol immediate release (IR) tablet | Drug: Metoprolol- Lopressor<br>* Immediate release tablet, Day 1 50 mg four times daily, Day 2, 3 and 4 100 mg twice daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile in terms of Cmax, Cmin, AUC | Assesment following multiple dosing of metoprolol CR/XL 200 mg once daily, or multiple dosing of metoprolol IR 200 mg daily in divided doses | Treatment duration: 4 days | 
| Pharmacodynamics in terms of Hourly means of heart rate (Holter recorded) | Assesment following multiple dosing of metoprolol CR/XL 200 mg once daily, or multiple dosing of metoprolol IR 200 mg daily in divided doses | Treatment duration: 4 days | 
| Safety profile in terms of adverse events |  | Treatment duration: 4 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metoprolol, acute myocardial infarction, pharmacokinetics, pharmacodynamics