Pharmacokinetic (Bioavailability) Studies of Magnesium Preparations

Abstract

In order to obtain valid results when studying the bioavailability of medicinal products containing magnesium salts, it is necessary to take into account endogenous levels of the macroelement in the body. The aim of the study was to conduct a systematic review of the results of clinical studies on the bioavailability of medicinal products containing magnesium, to evaluate the methods used for determining the endogenous level of magnesium, and to establish the necessity for adjusting pharmacokinetic parameters according to the identified endogenous magnesium levels. The review includes data from clinical studies of magnesium bioavailability performed with healthy volunteers and published over the past 5 years. According to the literature review results, the most commonly chosen primary endpoint is urinary magnesium excretion analysis, and the most secondary endpoint is plasma or serum magnesium determination. Data sources for the review included Google’s search engine; PubMed, UpTodate®, ClinicalTrials.gov databases; and official websites of regulatory authorities (EFSA, EMA, and FDA). In most studies, endogenous magnesium levels were taken into account at all blood sampling points, and this provided an opportunity to avoid errors and misinterpretations of the results. Adjustments of pharmacokinetic parameters with regard to endogenous magnesium values were performed differently. Some studies treated endogenous magnesium values as independent variables and compared the values obtained after drug administration with them; other studies treated endogenous magnesium values as a covariate influencing the values obtained and requiring mandatory consideration; two studies involved a classical adjustment of pharmacokinetic parameters, the subtraction of endogenous values from the values obtained after drug administration. The evaluation of endogenous magnesium levels as part of bioavailability studies is necessary to adjust pharmacokinetic parameters and to obtain valid study results. It should be planned beforehand at the time of preparation of the study protocol.