The Effect Of Hyperbaric Oxygen On The Pharmacokinetics Of Methotrexate And The Permeability Of Methotrexate Through The Blood-brain Barrier

1. To observe the effect of hyperbaric oxygen (HBO) on the pharmacokinetics of methotrexate(MTX):Methods:12 rabits were divided into two groups at random: HBO group and control group. All the animals were injected MTX 50 mg/kg into the ear vein.Then rabbits in HBO group breath 100% oxygen under hyperbaric condition (0.25MPa,90 min), and the rabbits in control group breath air under nornmal pressure condition for 90 min.1.5ml blood samples were taken at 0.25,0.5,1,2,4,8,12,24,36 h after drug injection and MTX in the plasma was determined with HPLC.Rresults:Compared with control group,there were no significant change of the pharmacokinetic parameters (p>0.05).There were no significant change of elimination half-life, but HBO groupcontrol group.There were no significant change of distribution half-life,but HBO groupcontrol group. Conclusion:The pharmacokinetics of methotrexate can not influenced by HBO condition (0.25 MPa ,90 min )The excretion of MTX from the renal increased in HBO group.HBO could enhance the activity of some enzymes ,so HBO increase the translation of membrane to MTX. HBO could increase the permeability of blood-brain barrier (BBB) to MTX,so HBO could enlarge the area of distribution of MTX.2. To observe the effect of hyperbaric oxygen on the permeability of methotrexate through the BBB:Methods:12 rabbits were divided equal into HBO group and control group at random:.Each rabbit was given a dose of MTX 100 mg/kg iv. After injection rabbits in HBO group breath 100% oxygen under hyperbaric condition (0.25MPa,90 min), and rabbits in control group breath air under nornmal pressure condition.Venous blood and cerebral-spinal fluid(CSF) were taken at 1.5h affter the drug administration.The concentrations of MTX. in the plasma and CSF was determined with HPLC(LC-6A)instrument.Results :After 1.5h of drug administration, the MTX concentration in the CSF was 2.67% of that in the plasma of the HBO group, while that of the control group was 1.24%,and significant difference was shown with paired t-test (p< 0.01)between the two groups. Conclusion: HBO could increase the permeability of BBB to MTX.