Magnesium deficiency can occur in several diseases. such
as malabsorption syndromes, diabetes mellitus and renal
disorders. It can be treated with oral magnesium compounds,
of which several preparations are currently available:
various complex salts, and the oxide or hydroxide of
magnesium [1]. In the present study, two formulations of
magnesium-L-asparate HCI (Magnesiocard® tablets and
Magnesiocard® granules, Verla-Phann, FRG) were compared with magnesium-oxide (Magnetrans® forte capsules, Fresenius, FRG) with respect to bioavailability, tolerability, and stool frequency.
The three magnesium preparations were each administered in an open manner to 3 groups of 8 healthy volunteers according to a parallel group design. The groups of 4 males and 4 females each were comparable with regard to age, height and body weight. After a control and a placebo period of one week, 60 mEq/d and 90 mEq/d magnesium were administered for 7 days each. No special diet was given. Cumulative urinary magnesium excretion was used to assess magnesium absorption [2. 3]. Plasma and urine concentrations of magnesium. potassium and
calcium were measured by atome emission spectromtryusing a Spectraspan SR (ARL). Urine pH was assessed with indicator strips (Spezialindikator pH 4.0-7.0. Merck. Darmstadt ). Stool frequency was evaluated by the volunteers, recording the time and number of stools. Mouth to caecum transit time was estimated using salazosulfapyridine
(SASP) as the test compound [4], measuring SP in saliva by a specific and selective HPLC method [5]. Means and SDs of the parameters were
calculated and tested by analysis of variance (ANOVA, randomized
factorial design) for differences. 95% confidence intervals were calculated for cumulative urinary magnesium excretion. For statistical analysis of stool frequency, the one criterion variance analysis of Kruskal and Wallis was applied [6]. During the higher magnesium dosage, stool frequency was increased 1.8-fold by magnesium-oxide, 3.2-fold by granules and 2.0-fold by tablets of magnesium-L-aspartate-HCI. The differences between the treatment groups did not reach statistical significance. Mean mouth-caecum transit time of about 4 h was not affected by magnesium treatment, suggesting that the magnesium preparations exerted their laxative effect mainly in the colon. Minor adverse effects were reported in each group, such as flatulence. diarrhoea, and gastric discomfort. There were complaints of an unpleasant taste of the granule formulation, which may influence patients compliance. Urine pH was decreased ( - 0.5) during magnesiumL-aspart ate-HCl and increased ( + 0.5) during magnesium-oxide (P < 0.01) administration, indicating a slight disturbance of the acid/base equilibrium. This aspect may be of clinical importance, particularly in elderly patients with multiple diseases. Calcium and potassium levels in plasma and urine were not altered by magnesium treatment. Plasma magnesium, remained unchanged too. The mean cumulative urinary magensium excretion was similar during the placebo and control periods, ranging from 77.5 to 93 .7 mEq/week. There was a significant increase during magnesium administra tion,more marked during the Mg-L-asparta te-HCl phase (P < 0.0001). The maximum value of 187.4 mEq/week was reached during treatment with magnesium-L-asparateHCI granules 90 mEq/d. The differences between the three treatment groups indicated better absorption of magnesium-L-asparate-HCI than of magnesium-oxide. One possible explanation might be the poor solubility of magnesium-oxide, which in water is 8.6 mg/di [7].
In conclusion, all three formulations of magnesium given in the trial were well tolerated, but they increased the number of stools. Magnesium-oxide showed significantly lower absorption than magnesium L-asparate-HCI.
As there were complaints of an unpleasant taste of the resuspended
granules, tablets of magnesium-L-aspartateHCI appear to be the first choice for magnesium substitution among the formulations investigated.
References
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( 1987) High performance liquid chromatographic assay of sulfapyridinc
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Cleveland. CRC Press, B-106