Pharmacokinetics and kinetic-dynamic modeling of an 8-aminoquinoline candidate anticyanide and antimalarial drug (WR242511)
Marino, M.T.; Peggins, J.O.; Brown, L.D.; Urquhart, M.R.; Brewer, T.G.
Drug Metabolism and Disposition the Biological Fate of Chemicals 22(3): 358-366
1994
ISSN/ISBN: 0090-9556 PMID: 8070311 Document Number: 429325
WR242511, an 8-aminoquinoline primaquine replacement and potential anticyanide compound, was studied in dogs under laboratory conditions. The drug's pharmacokinetics and pharmacodynamics are described for oral and intravenous dosing, and two kinetic-pharmacodynamic models are shown to describe the single dose data. A significant lag occurred between the onset of appearance of drug in the plasma and the onset of methemoglobinemia. Peak drug concentrations occurred within 4 hours of oral dosing, and peak effect (percentage methemoglobin) did not occur for 72 to 96 hours after both oral and intravenous routes. Elimination half-life for the drug was 30 +or-14 hours. Two kinetic-dynamic models, one with an effect compartment relating drug concentration to effect and one with metabolite causing a first-order conversion of haemoglobin to methemoglobin, were compared for their ability to predict multiple dose pharmacokinetics and pharmacodynamics and were both found to be useful.