Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects.

We conducted a single-center, double-blind, placebo-controlled phase I study in HIV-positive subjects to ascertain the safety, tolerance, bioavailability, pharmacokinetics, and maximum tolerated dose of HPMPC (cidofovir). Five subjects were randomized to receive drug and two to receive placebo at each of three dosage tier (1, 3, and 10 mg/kg) with a 2-week washout period doses. Subjects at 1 and 3 mg/kg received single doses of HPMPC by subcutaneous (s.

Acetylcholinesterase inhibition and anti-soman efficacy of homologs of physostigmine.

Inhibition of acetylcholinesterase (AChE) activity by physostigmine (PHY) is reversible due to spontaneous decarbamylation. Physostigmine has been shown to be effective as a pretreatment against potent anticholinesterase poisons (e.g.

Evaluation of several oximes as reactivators of unaged soman-inhibited whole blood acetylcholinesterase in rabbits.

The antidotal benefit of oximes against organophosphorus (OP) anticholinesterase intoxication is thought to be due to reactivation of the OP-inhibited acetylcholinesterase (AChE). This study was conducted to determine whether the antidotal efficacy against soman by the oximes 2-hydroxyiminomethyl-3-methyl-1-[2-(3-methyl-3-nitrobutyl oxymethyl)]-imidazolium Cl (ICD 467) and 1,1'-methylenebis[4-(hydroxyiminomethyl) pyridinium] di-Cl (MMB-4) resulted, in part, from reactivation of the inhibited AChE. These oximes were tested in parallel with pralidoxime Cl (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridinio-3-(4-carbamoyl-1-pyridinio+ ++)-2-oxapropane di-Cl (HI-6).

Acetylcholinesterase inhibition by (+)physostigmine and efficacy against lethality induced by soman.

The optical isomer (+)Physostigmine [(+)Phy] is a very weak anticholinesterase. In a recent report, pretreatment with (+)Phy, at a dose which failed to inhibit acetylcholinesterase (AChE), and atropine provided efficacy against a lethal dose of sarin (SYNAPSE:2, 139, 1988). It was of interest to see whether (+)Phy could protect against soman at a dose which caused only marginal inhibition of the whole blood (WB) AChE in guinea pigs (GPs).