Oral kinetics and bioavailability of the cholinesterase reactivator HI-6 after administration of 2 different formulations of tablets to dogs.
A one-compartment open model with first-order absorption was used for comparing new oral formulations of the potent acetylcholinesterase reactivating oxime HI-6. Although mean peak plasma levels did not differ between retard and conventional tablets (21.38 and 20.74 mumol/l), the time for reaching peak levels was significantly longer (5.5 h) with retard than with conventional tablets (2.86 h). Among other pharmacokinetic estimates only absorption half-lives and areas under the concentration-time curve (AUC) were significantly different (P less than 0.05). The AUC with retard tablets was 8.07% and that of conventional tablets 5.42% of intravenous AUC, indicating low bioavailability of oral HI-6 formulations. Potential therapeutic use of HI-6 requires, therefore, further investigations in order to improve its gastrointestinal absorption.
Maksimović
M
M
Military Technical Institute, Belgrade, Yugoslavia.
Jovanović
D
D
Kovacević
V
V
Bokonjić
D
D
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002801:Cholinesterase Reactivators / Q000493:pharmacokinetics*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D010091:Oximes; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; D013607:Tablets; C022870:asoxime chloride