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EZorb Calcium®   Calcium Aspartate Anhydrous

Pharmacokinetic 


Tang, J. F. & Deng, X. J. September 27, 2000
Pharmacokinetic Test of Calcium Aspartate Anhydrous

This study tests the metabolic mechanism and the pharmacokinetics on the changes of
calcium aspartate anhydrous in animal bodies over time. The results indicate that the
absorption metabolism of calcium aspartate anhydrous in rat intestine satisfied the One-
Chamber model. The absorption of calcium aspartate anhydrous was relatively slower but
more complete than that of other calcium agents tested, including calcium citrate, calcium
gluconate and calcium carbonate. This can be explained by the fact that the molecules of
calcium aspartate anhydrous are absorbed in the small intestine as opposed to that other
calcium compounds are ionized and absorbed in the stomach. The results confirm that
calcium aspartate anhydrous stays in serum for a longer time at a higher level. The peak
of serum calcium concentration arrived later (tmax =0.74hrs), but the half-life was longer
(t1/2 =4.22hrs) than those of other calcium agents. The area under curve (AUC0_t) is
201.75(µg/ml)•hr (see Fig. 1). The kinetic change of the calcium aspartate anhydrous
levels in the serum of household dogs and other dynamic parameters thereof are
consistent with those of rats.

1. Agents

(1) Calcium aspartate anhydrous, a white anhydrous powder containing 13% elemental
calcium, was formulated with 0.5% CMC to create solutions with calcium
concentration of 15mg/ml, 10mg/ml and 5mg/ml respectively.

(2) Calcium citrate, a white powder containing 20.3% of elemental calcium, was
formulated with 0.5% CMC into a mixed suspension with calcium concentration of
10mg/ml.

(3) Calcium gluconate, a white crystalline powder containing 8.9% of calcium, was
formulated with 0.5% CMC into a mixed suspension with 10mg/ml calcium
concentration.

(4) Calcium carbonate, a white powder containing 40.9% of calcium, was formulated
with 0.5% CMC into a mixed suspension which has a calcium concentration of
10mg/ml.

2. Animals and apparatus

(1) Animals: Wistar rats of male and female each weighing 150-170 g, 180-220 g
respectively, were provided by Department of Laboratory Animals, Shanghai Medical
University. Male crossbred domestic dogs each weighing 20.5-26.5kg, were provided by Laboratory Animals, Shanghai Chinese Medical University.
(2) Apparatus: Jarrell-Ash 810 Atomic Absorption Spectrophotometer was produced by
Jarrell Ash Corp.,USA; Centrifuge himac CR7 was produced by Hitachi, Japan; DT-100

Tang, J. F. & Deng, X. J. September 27, 2000

Single Pan Balance was produced by Beijing Optical Apparatus Factory; VM3 Vortex
Mixer was produced by Shanghai Guanghua Scientific Apparatus and Materials Co. Ltd.


3. Dosage and administration
The dosage administered to rats was designed for the following six groups:

(1) Group A: high dosage of calcium aspartate anhydrous in 2.31g/kg body weight
(containing 300mg calcium/kg body weight),
(2) Group B: medium dosage of calcium aspartate anhydrous in 1.54g/kg body weight
(containing 200mg calcium/kg body weight),
(3) Group C: low dosage of calcium aspartate anhydrous in 0.77g/kg body weight
(containing 100mg calcium/kg body weight),
(4) Group D: calcium citrate in a dosage of 0.98g/kg body weight (containing 200mg
calcium/kg body weight),
(5) Group E: calcium gluconate in a dosage of 2.25g/kg body weight (containing 200mg
calcium/kg body weight), and
(6) Group F: calcium carbonate in a dosage of 0.49g/kg body weight (containing 200mg
calcium/kg body weight).

The dosage of calcium aspartate anhydrous for dogs is 1.54g/kg body weight (containing
200mg calcium/kg body weight) in correspondence with that of the medium dosage
group of rats.

4. Test

(1) Determination of pharmacokinetic parameters
Sixty lab rats were randomly divided into six groups: the calcium aspartate anhydrous
group of high dosage, the calcium aspartate anhydrous group of medium dosage, the
calcium aspartate anhydrous group of low dosage, the calcium citrate group, the calcium
gluconate group and the calcium carbonate group. Twelve hours after the animals had
been fasted, 0.5ml plasma was sampled by excising eyeballs. The plasma was established
as the blank group. Then rats were administered agents once in an amount of 20ml/kg
body weight by pouring into the stomach. 0.5ml plasma was sampled by taking from
eyeballs 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 16 hours later after the administration. The
plasma was left for 30 minutes at room temperature and was then centrifuged at 300rpm
for 20 minutes. 0.2ml serum was sampled, diluted to 2ml with lanthanum diluents, and
homogenized. The concentration of calcium was measured by the Atomic Absorption
Spectrophotometer.

(2) Measurement of calcium aspartate anhydrous level in dog serum


Tang, J. F. & Deng, X. J. September 27, 2000

Five domestic dogs were administered agents once in an amount of 200ml/kg body
weight by pouring into the stomach. 0.5ml blood was sampled respectively from femur
vein 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours later after the administration. The blood was left for 30 minutes at room temperature and was then centrifuged at 300rpm for 20
minutes. 0.2ml serum was sampled, diluted to 2ml with lanthanum diluents, and
homogenized. The solution is stored for measurement.


5. Results
(1) Pharmacokinetic parameters
(i) The enhancement of serum Ca level at various time after the administration of agents was shown in Table I, Fig. 1 and Fig. 2.

                                     Table I. Serum Ca Level Increase vs. Time

Serum Ca Picture

* Group A: high dosage of calcium aspartate anhydrous
B: medium dosage of calcium aspartate anhydrous
C: low dosage of calcium aspartate anhydrous
D: calcium citrate
E: calcium gluconate
F: calcium carbonate

Fig. 1 Serum Ca Level Increase By Dosage of Calcium Aspartate Anhydrous
Serum Increase Picture
Tang, J. F. & Deng, X. J September 27, 2000
Fig. 2 Serum Ca Level Increase Over Time
Serum Ca Increase over time Picture

(ii) The experimental data was fitted by computer with SAS Statistical Software, and the following pharmacokinetics parameters was obtained: half-life of clearance t1/2 =4.22 hr, area under the curve AUC=201.75 (µg/ml)•hr, maximum value of serum Ca Cmax =32.30 µg/ml, time for arriving the maximum tmax =0.74 hr.


              Table II. Pharmacokinetics parameters of various calcium preparations

pharmacokinetics parameters Picture

(2) Measurement of calcium aspartate anhydrous level in the serum of dog and computation of pharmacokinetics parameters

Serum Ca levels at various time after administration were shown in Table III, the pharmacokinetics parameters fitted were listed in Table IV.

Tang, J. F. & Deng, X. J September 27, 2000
Table III. Serum Ca Levels in Dogs at Various Time After Administration
Serum Ca Increase over time Picture

6. Conclusion

It is demonstrated that calcium aspartate anhydrous has longer metabolic time and higher
bioavailability, which make the formation of bone Ca more efficient and effective. This
brings about a net increase of bone matrix and realizes the objective to prevent and treat
osteoporosis.


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