Sandbox Reserved 1474: Difference between revisions

Line 72:

====Effect of mAb6H4 on METH and AMP pharmacokinetics====

the t1/2lamdaZ of mAb6H4 is reported to be 8 days<>, and the METH induced behavior effects on locomotor effects is within 400 min after METH administration for the maximum dosage (3.0mg/kg) reported<>. Thus to compare the disposition of drugs with or without mAb6H4, ~~AUC4~~.5h 38min was used because it was not possible to conduct complete pharmacokinetic profile for 8 days.

the t1/2lamdaZ of mAb6H4 is reported to be around 8 days<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, and the METH induced behavior effects on locomotor effects is within 400 min after METH administration for the maximum dosage (3.0mg/kg) reported<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Thus to compare the disposition of drugs with or without mAb6H4, AUC 4.5h 38min <<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>>was used because it was not possible to conduct complete pharmacokinetic profile for 8 days.

For METH doses of 0.3mg/kg and 1 mg/kg in rats, administration of mAb6H4 has led to significantly higher serum concentrations corresponding to significantly lower brain concentration of METH<> during the time frame with the drug dose was less than the mAb6H4 binding capacity. It was obvious that mAb6H4 administration initially caused a rapid efflux of METH from the brain due to its high affinity, however, compared to METH concentration in the brain without mAb6H4, after 4.5 hours, there seems to be a very slight rebound of the concentration in the brain. The reason is unknown, and could be explained as slower redistribution of the drug from other tissues. Yet, however, at this point, even with the rebound, both the METH concentration in control and in the animals administered with mAb6H4 are well below the threshold associated with increased locomotor activity.

For METH doses of 0.3mg/kg <ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>and 1 mg/kg <ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>in rats, administration of mAb6H4 has led to significantly higher serum concentrations corresponding to significantly lower brain concentration of METH<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> during the time frame with the drug dose was less than the mAb6H4 binding capacity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. It was obvious that mAb6H4 administration initially caused a rapid efflux of METH from the brain due to its high affinity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, however, compared to METH concentration in the brain without mAb6H4, after 4.5 hours, there seems to be a very slight rebound<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> of the concentration in the brain. The reason is unknown, and could be explained as slower redistribution of the drug from other tissues<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Yet, however, at this point, even with the rebound, both the METH concentration in control and in the animals administered with mAb6H4 are well below the threshold associated with increased locomotor activity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.

mAb6H4 also appeared to have more mild effect to AMP<> because it had little cross activity with AMP in vitro. It was explained possibility because increased the amounts of METH in the serum available for metabolism.

mAb6H4 also appeared to have more mild effect to AMP<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> because it had little cross activity with AMP in vitro. It was explained possibility because increased the amounts of METH in the serum available for metabolism<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.

However, for METH dose of 3.0mg/kg, which was greater than the mAb6H4 binding capacity, METH induced locomotor effects appeared to be increased<>. Although there are possible explanations, the reason remained to be understood<>. The idea that mAb may slow the input of METH while prolonging exposure is proposed.

However, for METH dose of 3.0mg/kg<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, which was greater than the mAb6H4 binding capacity, METH induced locomotor effects appeared to be increased<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Although there are possible explanations, the reason remained to be understood<>. The idea that mAb may slow the input of METH while prolonging exposure is proposed<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.

Sandbox Reserved 1474: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 72: / Line 72: @@
 ====Effect of mAb6H4 on METH and AMP pharmacokinetics====
-the t1/2lamdaZ of mAb6H4 is reported to be 8 days<>, and the METH induced behavior effects on locomotor effects is within 400 min after METH administration for the maximum dosage (3.0mg/kg) reported<>. Thus to compare the disposition of drugs with or without mAb6H4, AUC4.5h 38min was used because it was not possible to conduct complete pharmacokinetic profile for 8 days.
+the t1/2lamdaZ of mAb6H4 is reported to be around 8 days<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, and the METH induced behavior effects on locomotor effects is within 400 min after METH administration for the maximum dosage (3.0mg/kg) reported<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Thus to compare the disposition of drugs with or without mAb6H4, AUC 4.5h 38min <<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>>was used because it was not possible to conduct complete pharmacokinetic profile for 8 days.
-For METH doses of 0.3mg/kg and 1 mg/kg in rats, administration of mAb6H4 has led to significantly higher serum concentrations corresponding to significantly lower brain concentration of METH<> during the time frame with the drug dose was less than the mAb6H4 binding capacity. It was obvious that mAb6H4 administration initially caused a rapid efflux of METH from the brain due to its high affinity, however, compared to METH concentration in the brain without mAb6H4, after 4.5 hours, there seems to be a very slight rebound of the concentration in the brain. The reason is unknown, and could be explained as slower redistribution of the drug from other tissues. Yet, however, at this point, even with the rebound, both the METH concentration in control and in the animals administered with mAb6H4 are well below the threshold associated with increased locomotor activity.
+For METH doses of 0.3mg/kg <ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>and 1 mg/kg <ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>in rats, administration of mAb6H4 has led to significantly higher serum concentrations corresponding to significantly lower brain concentration of METH<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> during the time frame with the drug dose was less than the mAb6H4 binding capacity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. It was obvious that mAb6H4 administration initially caused a rapid efflux of METH from the brain due to its high affinity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, however, compared to METH concentration in the brain without mAb6H4, after 4.5 hours, there seems to be a very slight rebound<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> of the concentration in the brain. The reason is unknown, and could be explained as slower redistribution of the drug from other tissues<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Yet, however, at this point, even with the rebound, both the METH concentration in control and in the animals administered with mAb6H4 are well below the threshold associated with increased locomotor activity<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.
-mAb6H4 also appeared to have more mild effect to AMP<> because it had little cross activity with AMP in vitro. It was explained possibility because increased the amounts of METH in the serum available for metabolism.
+mAb6H4 also appeared to have more mild effect to AMP<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/> because it had little cross activity with AMP in vitro. It was explained possibility because increased the amounts of METH in the serum available for metabolism<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.
-However, for METH dose of 3.0mg/kg, which was greater than the mAb6H4 binding capacity, METH induced locomotor effects appeared to be increased<>. Although there are possible explanations, the reason remained to be understood<>. The idea that mAb may slow the input of METH while prolonging exposure is proposed.
+However, for METH dose of 3.0mg/kg<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>, which was greater than the mAb6H4 binding capacity, METH induced locomotor effects appeared to be increased<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>. Although there are possible explanations, the reason remained to be understood<>. The idea that mAb may slow the input of METH while prolonging exposure is proposed<ref name="Pharmacodynamic mechanisms of monoclonal antibody-based antagonism of (+)-methamphetamine in rats"/>.