8
Views
4
CrossRef citations to date
0
Altmetric
Original Article

Effect of whole-body hyperthermia on the pharmacokinetics and toxicity of lonidamine in dogs

, , , &
Pages 531-544 | Received 01 Dec 1993, Accepted 29 Nov 1994, Published online: 09 Jul 2009
 

Abstract

The pharmacokinetics and toxicity of intravenous lonidamine were investigated in dogs receiving four cycles of lonidamine (400 or 800 mg/m2) ± whole-body hyperthermia (WBH). Clearance and volume of distribution in dogs receiving lonidamine during WBH increased 1·6–2·3 and 1·9–3·5-fold respectively, relative to dogs receiving lonidamine under euthermic conditions (p < 0·02). In dogs receiving lonidamine under euthermic conditions or 400 mg/m2 + WBH, the area under the lonidamine concentration versus time curve (AUC) measured during the fourth treatment was 21–58% lower than the first treatment AUC. However, in dogs receiving 800 mg/m2 + WBH, the fourth treatment AUC was four-fold higher than the first treatment AUC (p < 0·02). This suggests repeated exposure to 800 mg/m2 lonidamine and WBH impairs lonidamine metabolism. Weakness, hypoglycaemia, and elevations in amylase, alanine aminotransferase, alkaline phosphatase and bilirubin were more severe or occurred exclusively in dogs receiving 800 mg/m2 + WBH. Since these changes were attributable to marked AUC increases, which occurred secondary to repeated exposure to 800 mg/m2 lonidamine during WBH, 400 mg/m2 was identified as the maximum tolerable dose to be administered intravenously to dogs during WBH.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.