Pharmacokinetics of intramuscularly administered biperiden in guinea pigs challenged with soman.
Biperiden is an anticholinergic compound that has demonstrated effectiveness for treating organophosphate-induced seizure/convulsions. The plasma levels of biperiden associated with this efficacy have not yet been defined. In this study, the pharmacokinetics and tissue distribution of biperiden after intramuscular administration of 0.5 mg/kg were conducted while monitoring pharmacodynamic (electroencephalographic) data in soman-exposed guinea pigs. Overall, 59% of the animals had seizures terminated within 30 min of the biperiden administration. The mean time to seizure termination was 15.9 min. The pharmacokinetics of biperiden after i.m. administration to guinea pigs were best described by a one-compartment model with first-order absorption and elimination. The maximal plasma biperiden concentration (34.4 ng/mL) in seizure-terminated animals occurred at 26.3 min. Extensive partitioning into peripheral tissues was noted supporting the relatively large volume of distribution observed. Maximal biperiden concentrations in the cortex and brain stem were found at 30 min and were 2.3 and 1.7 times greater, respectively, than that in plasma. The time for maximal plasma concentration was found to corresponded well with the mean time to seizure termination following drug administration.
Capacio
B R
BR
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA. benedict.capacio@amedd.army.mil
Byers
C E
CE
Caro
S T
ST
McDonough
J H
JH
D000818:Animals; D001712:Biperiden / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004569:Electroencephalography; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D008297:Male; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012999:Soman / Q000633:toxicity*; D014018:Tissue Distribution
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D001712:Biperiden; D012999:Soman