Comparative anticonvulsant potency and pharmacokinetics of (+)-and (-)-enantiomers of stiripentol.

The anticonvulsant potency and pharmacokinetics of the enantiomers of stiripentol were compared using the intravenous pentylenetetrazol infusion seizure model in the rat. Enantioselectivity was observed with respect to both the anticonvulsant activity and elimination kinetics of this compound. (+)-Stiripentol was 2.

Efficacy of stiripentol in the intravenous pentylenetetrazol infusion seizure model in the rat.

The potential effectiveness of stiripentol, a new allylic alcohol anticonvulsant, against generalized epilepsy of the absence type was evaluated in the intravenous pentylenetetrazol (PTZ) infusion seizure model in the rat. The ability of stiripentol to elevate the threshold dose of PTZ in eliciting clonic seizure (i.e.

Alteration in the disposition and metabolism of S(-)-propranolol in rats with active respiratory viral infection.

Viral illness elicited marked changes in the disposition and metabolism of S(-)-propranolol in rats during the course of a recent viral outbreak in our rodent colony. A slower rate of gastrointestinal absorption and a much higher clearance of orally-administered S(-)-propranolol were observed. The apparent increase in metabolic clearance is partly attributed to a decrease in the serum protein binding of S(-)-propranolol.

Remission induction of meningeal leukemia with high-dose intravenous methotrexate.

Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L.

Altered central nervous system pharmacology of methotrexate in childhood leukemia: another sign of meningeal relapse.

CSF and plasma antifolate concentrations during 257 intravenous (IV) infusions of high-dose methotrexate were measured in 60 children with acute lymphoblastic leukemia. In 49 children who have never had evidence for CNS leukemia, the mean steady-state CSF to plasma methotrexate ratio was 0.013 (SD = 0.

Pharmacokinetics of oral methotrexate in children.

The absorption and disposition kinetics of p.o. methotrexate were studied in 15 children.

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species.