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Disposition of a single oral dose of a cannabidiol medication in healthy cats.

ABSTRACT: The historical use of the marijuana plant for medicinal purposes is long. One of the historical uses has been for the treatment of epilepsy. Recently, the Food and Drug Administration has approved a highly purified cannabidiol medication for the add on therapy in people with certain forms of epilepsy. With the increase interest of the use of cannabidiol in the veterinary community, the aim of this study was to describe the disposition of a single dose of a cannabidiol medication in healthy cats in both the fed and fasted state. Pharmacokinetic analysis reveals that relative bioavailability of cannabidiol shows a near eleven-fold increase when administered in the fed state compared to the fasted state. Additionally, concentrations achieved at a dose of 5 mg/kg, may be sufficient to explore the therapeutic potential in cats with epilepsy.

SUBMITTER: Jukier T

PROVIDER: S-EPMC10251743 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Disposition of a single oral dose of a cannabidiol medication in healthy cats.

Jukier Tom T Cruz-Espindola Crisanta C Martin Doug D Boothe Dawn M DM

Frontiers in veterinary science 20230526

The historical use of the marijuana plant for medicinal purposes is long. One of the historical uses has been for the treatment of epilepsy. Recently, the Food and Drug Administration has approved a highly purified cannabidiol medication for the add on therapy in people with certain forms of epilepsy. With the increase interest of the use of cannabidiol in the veterinary community, the aim of this study was to describe the disposition of a single dose of a cannabidiol medication in healthy cats ...[more]

PMID: 37303724

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Project description:Treatment of schistosomiasis relies precariously on just one drug, praziquantel (PZQ). In the search for alternatives, 15 S-[2-(alkylamino)alkane] thiosulfuric acids were obtained from a previous research program and profiled in mice for efficacy against both mature (>42-day-old) and juvenile (21-day-old) Schistosoma mansoni using a screening dose of 100 mg/kg PO QDx4. One compound, S-[2-(tert-butylamino)-1-phenylethane] thiosulfuric acid (TPT sulfonate), was the most effective by decreasing female and male worm burdens by ≥ 90% and ≥46% (mature), and ≥89% and ≥79% (juvenile), respectively. In contrast, PZQ decreased mature female and male worm burdens by 95% and 94%, respectively, but was ineffective against juvenile stages. Against 7-day-old lung-stage worms, TPT sulfonate was only effective at twice the dose decreasing female and male burdens by 95 and 80%, respectively. Single oral doses at 400 and/or 600 mg/kg across various developmental time-points (1-, 7-, 15-, 21- and/or 42 day-old) were consistent with the QD x4 data; efficacy was strongest once the parasites had completed lung migration, and female and male burdens were decreased by at least 90% and 80%, respectively. In vitro, TPT sulfonate is inactive against the parasite suggesting a pro-drug mechanism of action. In mice, TPT sulfonate is fully absorbed and subject to rapid, non-CYP-mediated, first-pass metabolism that is initiated by desulfation and yields a series of metabolites. The initially-formed free thiol-containing metabolite, termed TP thiol, was chemically synthesized; it dose-dependently decreased S. mansoni and Schistosoma haematobium motility in vitro. Also, when administered as a single 50 mg/kg IP dose, TP thiol decreased 33-day-old S. mansoni female and male burdens by 35% and 44%, with less severe organomegaly. Overall, TPT sulfonate's efficacy profile is competitive with that of PZQ. Also, the characterization of a parasiticidal metabolite facilitates an understanding and improvement of the chemistry, and identification of the mechanism of action and/or target.

Dataset Information

Disposition of a single oral dose of a cannabidiol medication in healthy cats.

Publications

Disposition of a single oral dose of a cannabidiol medication in healthy cats.

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