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J Clin Pharmacol. 1990 Feb;30(2 Suppl):S2-16.

Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article.

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Pharmaceutical Research and Development, AB Hässle, Mölndal, Sweden.


In the development of a new controlled release preparation and its subsequent assessment there are a number of factors that need to be considered both related to the drug itself and to the pharmaceutical preparation. This review describes the biopharmaceutical and pharmacokinetic properties of metoprolol CR/ZOK, a recently introduced formulation of a widely used beta 1-selective adrenoceptor antagonist intended for once daily usage. The metoprolol CR/ZOK preparation provides reproducible dissolution and absorption properties resulting in stable plasma concentrations with minimum fluctuations over a 24-hour dosage interval. This has been shown in extensive studies comprising over 200 healthy volunteers. Considerations for a new drug preparation such as bioavailability and variability in relation to a standard treatment and the clinical significance of taking the drug with food and in increasing doses, are potential concerns that do not seem to be a problem for the therapeutic use of metoprolol CR/ZOK. Furthermore, the pharmacokinetic data achieved in young healthy subjects appear to be relevant for the treatment of patients, as shown by the consistent plasma concentration profiles obtained in elderly and in hypertensive patients.

[Indexed for MEDLINE]

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