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Valproic acid pharmacokinetics in the mouse following controlled‐release of pharmacologic and toxic doses via novel implantable and refillable drug reservoirs
Author(s) -
Nau Heinz,
Finley Paul,
Williams Jane,
Brendel Klaus
Publication year - 1983
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510040209
Subject(s) - valproic acid , pharmacokinetics , drug , pharmacology , silastic , medicine , plasma concentration , membrane , chemistry , anesthesia , epilepsy , biochemistry , psychiatry
Novel drug reservoirs are described which, after their implantation under mouse skin, continuously released organic liquids such as the anti‐epileptic drug valproic acid at preselected rates for periods up to several weeks. The liquids, which were filled into the reservoirs, diffused through silastic membranes. The area and thickness of these membranes determined the administered dose. Administration of the anti‐epileptic drug valproic acid at various selected doses resulted in persistent drug concentrations spanning from subtherapeutic to toxic levels. The drug reservoirs were easily refillable in situ which greatly extended the duration of the experiment. The dose administered could be determined within 5–15 per cent (rel. S.D.). It is suggested that the maintenance of persistent drug levels in small laboratory animals may be an appropriate model for the pharmacological and toxicological study of those compounds with short half‐lives and high clearance rates in these species.