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Biomedical subjects

D Bokonjić

Publications and source records attributed to D Bokonjić.

4 recordsLinked to original sources
PubMed1991

Anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by highly toxic organophosphorus compounds.

The aim of this study was to compare the anticonvulsive and protective effects of diazepam and midazolam in rats poisoned by chemical warfare agents. In rats treated with soman, sarin or VX, the anticonvulsive effects of midazolam and diazepam were of similar magnitude. Atropine and oxime HI-6 decreased the toxicity of soman, sarin and VX 1.65, 2.06 and 18.3 times, respectively. The introduction of diazepam and midazolam in the therapy of rats poisoned by VX and sarin led to further improvement of protective indices. Midazolam was even more effective than diazepam. A reliable protective effect was obtained with the lowest dose of both benzodiazepines used (0.5 mg/kg). The specific benzodiazepine antagonist flumazenil abolished, almost completely, the protective effect of both benzodiazepines. These data confirmed a significant role of the gabaergic system in poisoning with organophosphorus compounds, especially during the initial stage of intoxication.

Animals↗
PubMed1987

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.

Administration, Oral↗
PubMed1987

Protective effects of oximes HI-6 and PAM-2 applied by osmotic minipumps in quinalphos-poisoned rats.

Protective and reactivating effects of oximes HI-6 and PAM-2, combined with atropine and diazepam, were investigated in quinalphos-poisoned rats. In protective experiments, atropine and diazepam decreased acute toxicity of the insecticide 3.3 times. Later administration of a single injection of oximes led to further improvement of protective indexes which were 1.45 (PAM-2) and 1.52 (HI-6) times larger. Plasma HI-6 concentrations below 1 microgram/ml, continuously maintained by osmotic minipumps and supported by a single administration of atropine and diazepam, protected animals from 18.6 LD50 of quinalphos, while its higher concentrations (ranging from 1 to 5.4 micrograms/ml) provided markedly better protection (up to 72 LD50). Corresponding plasma PAM-2 concentrations were even more effective in overcoming toxic effects of quinalphos. PAM-2 concentrations, continuously maintained in plasma, were distinctly better in protecting and reactivating peripheral cholinesterase activity than corresponding HI-6 concentrations in the case of quinalphos poisoning. On the basis of our findings we suggest that continuous maintenance of low oxime concentrations is preferred to single oxime administration in the therapy of organophosphate intoxications.

Animals↗