10/08/2008

Toxicity and Safety - Plasmatic concentration

• Plasmatic concentration in rats

 

The main objective of this study was the evaluation of magnesium plasmatic concentration at various P-MAPA doses.

 

Experimental  design 

 

 

 Three different doses were selected:

 

 375 (LD), 750 (MD) and 1500 (HD) mg/kg intraperitoneal administered into the rats.

 

Periods selected were 0.5, 1, 2, 4, 8, 12, 24, 36, 48 and 72 h. All the animals were left starving for 12 h before P-MAPA administration.

 

P-MAPA was suspended in PBS-A buffer (pH 7.2), immediately before the P-MAPA administration to animals which were previously weighted.

 

The suspension was administered in a dose/volume ratio of 10 ml/kg of animal weight, intraperitoneal.

 

After a selected period of time , animals were anaesthetized with ether and a blood sample was taken from the ocular plexus using a heparinized capillary.

 

The blood collected was then centrifuged at 3000 rpm for serum separation. Animals at this stage were sacrificed. The serum was treated with hydrogen peroxide and sulfuric acid. Water was added to the digested sample and the magnesium ions were determined by atomic absorption technique.

 

• In the three selected doses a rapid appearance of magnesium ions occurred (around 1 h) and then a slowly disappearance kinetics was exhibited.

 

• The magnesium ion content in non inoculated rats was 37.5 ± 4.95 ug/mL.

 

• Cmax(plasma level at 1 h after inoculation) averaged 87.8 ± 14.5 ug/mL, 71.3 ± 8.49 u/mL, and 53.8 ± 2.47 ug/mL for HD, MD and LD, respectively

 

• Cmin (plasma level at 12 h after start the inoculation) averaged 49.5 ± 7.78 ug/mL, 43.0 ± 1.77 ug/mL and 40.0 ± 1.80 ug/mL for HD, MD and LD, respectively.

 

• The plasma half life (t1/2) at HD was around 2.30 h