Pharmacokinetics in animals and humans of a first-in-class peptide deformylase inhibitor.

BB-83698, a potent and selective inhibitor of peptide deformylase, was the first compound of this novel antibacterial class to progress to clinical trials. Single- and/or multiple-dose studies with doses ranging from 10 to 50 mg of BB-83698/kg of body weight were done with mice, rats, and dogs. Intravenous pharmacokinetics were characterized by low to moderate clearances and moderate volumes of distribution for all species.

Pharmacokinetics of the antimalarial drug, AQ-13, in rats and cynomolgus macaques.

The purpose of this study was to evaluate the bioavailability and pharmacokinetics of a new antimalarial drug, AQ-13, a structural analog of chloroquine (CQ) that is active against CQ-resistant Plasmodium species, in rats and cynomolgus macaques. Sprague-Dawley rats (n = 4/sex) were administered a single dose of AQ-13 intravenously (i.v.

Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide deformylase inhibitor.

Objective: BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models.

Methods: MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays.

Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion.

In a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain-deleted human factor VIII (hFVIII) gene. Infusions were well tolerated. Tests for replication competent retrovirus have been negative.

Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane in rat plasma. II. Pharmacokinetic profile in male and female Sprague-Dawley rats evaluated by capillary electrophoresis.

This paper describes a pharmacokinetic study performed in Sprague-Dawley rats after i.v. administration of a single 6-mg/kg dose of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane (Altropane).

Contradistinction between doxorubicin and epirubicin: in-vivo metabolism, pharmacokinetics and toxicodynamics after single- and multiple-dosing in rats.

There is compelling in-vitro evidence that the evaluation of doxorubicin or epirubicin pharmacokinetics based solely on plasma concentration may not fully elucidate the differences between the two drugs. Both compounds bind to erythrocytes and their different binding to haemoglobin may influence their disposition in the body. The purpose of the present study was to compare the pharmacokinetics and metabolism of doxorubicin and epirubicin based on the plasma concentration, amount associated with blood cells and simultaneous monitoring of biliary and urinary elimination of unchanged drug and metabolites after single- and multiple-dose injections.

Contradistinction between doxorubicin and epirubicin: in-vitro interaction with blood components.

The molecular structure and anti-tumour activity of doxorubicin and epirubicin are similar. However, the incidence of their cardiotoxicity occurs at different cumulative dose concentrations. The purpose of this study was to investigate the in-vitro interaction of these two drugs with different blood components, namely intact erythrocytes, haemoglobin and erythrocyte ghosts.