Eur J ClinPharmacol(1991) 40:437-438

003169709100108G

© Springer-Verlag1991

Magnesium-L-aspartate-HCl and magnesium-oxide:

bioavailability in healthy volunteers
B. M i i h l b a u e r 1, M. S c h w e n k 1, W . M . Coram 2, K . H . A n t o n i n 1, P. E t i e n n e 2, P. R. B i e c k 1, and E L. D o u g l a s 2

Human PharmacologyInstitute, Ciba-GeigyGmbH,Tt~bingen,FRG

2 PharmaceuticalsDivision,Ciba-GeigyCorporation,SummitNJ, USA
Received:January 28, 1990/Acceptedin revisedform: October 19, 1990

K e y words: Magnesium deficiency, oral replacement ther- During the higher magnesium dosage, stool frequency
apy, bioavailability, adverse effects was increased 1.8-fold by magnesium-oxide, 3.2-fold by
granules and 2.0-fold by tablets of magnesium-L-aspar-
tate-HC1. The differences between the treatment groups
did not reach statistical significance. Mean mouth-caecum
Magnesium deficiency can occur in several diseases, such transit time of about 4 h was not affected by magnesium
as malabsorption syndromes, diabetes mellitus and renal treatment, suggesting that the magnesium preparations
disorders. It can be treated with oral magnesium com- exerted their laxative effect mainly in the colon. Minor ad-
pounds, of which several preparations are currently avail- verse effects were reported in each group, such as fla-
able: various complex salts, and the oxide or hydroxide of tulence, diarrhoea, and gastric discomfort. There were
magnesium [1]. In the present study, two formulations of complaints of an unpleasant taste of the granule formula-
magnesium-L-asparate HCI (MagnesiocardR tablets and tion, which may influence patients compliance.
MagnesiocardR granules, Verla-Pharm, FRG) were com- Urine pH was decreased ( - 0.5) during magnesium-
pared with magnesium-oxide (Magnetrans a forte cap- L-aspartate-HC1 and increased (+ 0.5) during magne-
sules, Fresenius, FRG) with respect to bioavailability, sium-oxide (P < 0.01) administration, indicating a slight
tolerability, and stool frequency. disturbance of the acid/base equilibrium. This aspect may
The three magnesium preparations were each adminis- be of clinical importance, particularly in elderly patients
tered in an open manner to 3 groups of 8 healthy volun- with multiple diseases. Calcium and potassium levels in
teers according to a parallel group design. The groups of plasma and urine were not altered by magnesium treat-
4 males and 4 females each were comparable with regard ment. Plasma magnesium, remained unchanged too.
to age, height and body weight. After a control and a The mean cumulative urinary magensium excretion
placebo period of one week, 60 mEq/d and 90 mEq/d (Tab. 1) was similar during the placebo and control peri-
magnesium were administered for 7 days each. No special ods, ranging from 77.5 to 93.7 mEq/week. There was a
diet was given. Cumulative urinary magnesium excretion significant increase during magnesium administration,
was used to assess magnesium absorption [2, 3]. Plasma more marked during the Mg-L-aspartate-HC1 phase
and urine concentrations of magnesium, potassium and (P < 0.0001). The maximum value of 187.4 mEq/week was
calcium were measured by atome emission spectrometry
using a Spectraspan 5R (ARL). Urine pH was assessed
with indicator strips (Spezialindikator pH 4.0-7.0, Merck, Table 1. Total 7 day cumulative urinary magnesium excretion
Darmstadt). Stool frequency was evaluated by the volun- (mEq/24 h * 7d) duringadministrationof Mg-L-aspartate-HC1(gra-
teers, recording the time and number of stools. Mouth to nules and tablets) and Mg-oxidecapsulesin comparisonwithcontrol
(no treatment) and placebo. Mean values (95% confidenceinter-
caecum transit time was estimated using salazosulfapy- vals) in 8 volunteersare give
ridine (SASP) as the test compound [4], measuring SP in
saliva by a specific and selective HPLC method [5]. Periods days 0-7 days 8-14 days15-21 days22-28
Treatment/dose control placebo 60 mEq/d 90mEq/d
Means and SDs of the parameters were calculated and
tested by analysis of variance (ANOVA, randomized fac- Mg-L-aspartate- 78 84 146 181
torial design) for differences. 95% confidence intervals HC1tablets (54-101) (59-110) (108-184) (137-225)
were calculated for cumulative urinary magnesium excre- Mg-L-aspartate- 91 81 156 187
tion. For statistical analysis of stool frequency, the one HCl-granules (61-120) (56-106) (113-199) (151-224)
criterion variance analysis of Kruskal and WaUis was ap- Mg-oxide 94 90 133 137
plied [6]. capsules (76-111) (74-105) (111-155) (115-159)
438 B. Mt~hlbauer et al.: Bioavailability of magnesium

r e a c h e d during t r e a t m e n t with m a g n e s i u m - L - a s p a r a t e - 2. Drenick E J, Hunt IF, Swendseid ME (1969) Magnesium depletion

HC1 granules 90 mEq/d. T h e differences b e t w e e n the
three t r e a t m e n t groups indicated better absorption of
magnesium-L-asparate-HC1 than of magnesium-oxide.
O n e possible explanation might be the p o o r solubility of
magnesium-oxide, which in water is 8.6 mg/dl [7].
In conclusion, all three formulations of m a g n e s i u m
given in the trial were well tolerated, but they increased
the n u m b e r of stools. Magnesium-oxide s h o w e d signifi-
cantly lower absorption than m a g n e s i u m L-asparate-HC1.
As there were complaints of an unpleasant taste of the re-
suspended granules, tablets of m a g n e s i u m - L - a s p a r t a t e -
HC1 a p p e a r to be the first choice for m a g n e s i u m substitu-
tion a m o n g the formulations investigated.
during prolonged fasting of obese males. J Clin Endocrinol Metab
29:1341-1348
3. Lim P, Jacob E (1972) Magnesium status of alcoholic patients. Me-
tabolism 21:1045-1051
4. Kennedy M, Chinwah R Wade DN (1979) A pharmacological
method of measuring mouth to caecum transit time in man. Br J
Clin Pharmacol 8:372-373
5. Owerbach J, Johnson NF, Bates TR, Pieniaszek HJ, Jusko WJ
(1987) High performance liquid chromatographic assay of sulfa-
pyridine and acetylsulfapyridine in biological fluids. J Pharm Sci
67:250-253
6. Kruskal WH, Wallis WA (1952) Use of ranks in one-criterion vari-
ance analysis. J Am Stat Assoc 47:583-621
7. Weast RC (1975) Handbook of chemistry and physics, 55th ed.
Cleveland, CRC Press, B-106

References
B. Mfihlbauer, M. D.
1. Mudge GH, Weiner IM (1990) Agents affecting volume and com- Human Pharmacology Institute (HPI)
position of body fluids. In: Gilman AG, Rall TW, Nies AS, Taylor Ciba-Geigy GmbH
P (eds) The pharmacological basis of therapeutics 8th ed., Perga- Waldh/Srnlestrage 22
mon, New York, pp 682-707 W-7400 Tt~bingen, FRG

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