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Mar. Drugs 2017, 15(6), 159; doi:10.3390/md15060159

A Study of 11-[3H]-Tetrodotoxin Absorption, Distribution, Metabolism and Excretion (ADME) in Adult Sprague-Dawley Rats

1
Department of Materials Science and Engineering, College of Materials, Xiamen University, Xiamen 361005, China
2
Engineering Research Center of Marine Biological Resource Comprehensive Utilization, Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005, China
3
Department of Inspection and Quarantine of Goods, Pingtan Entry-Exit Inspection & Quarantine Bureau of P.R.C, Pingtan 350400, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Andrew Turner
Received: 23 April 2017 / Revised: 19 May 2017 / Accepted: 25 May 2017 / Published: 2 June 2017
(This article belongs to the Special Issue Tetrodotoxin)
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Abstract

Tetrodotoxin (TTX) is a powerful sodium channel blocker that in low doses can safely relieve severe pain. Studying the absorption, distribution, metabolism and excretion (ADME) of TTX is challenging given the extremely low lethal dose. We conducted radiolabeled ADME studies in Sprague-Dawley rats. After a single dose of 6 μg/(16 μCi/kg) 11-[3H]TTX, pharmacokinetics of plasma total radioactivity were similar in male and female rats. Maximum radioactivity (5.56 ng Eq./mL) was reached in 10 min. [3H]TTX was below detection in plasma after 24 h. The area under the curve from 0 to 8 h was 5.89 h·ng Eq./mL; mean residence time was 1.62 h and t½ was 2.31 h. Bile secretion accounted for 0.43% and approximately 51% of the dose was recovered in the urine, the predominant route of elimination. Approximately 69% was recovered, suggesting that hydrogen tritium exchange in rats produced tritiated water excreted in breath and saliva. Average total radioactivity in the stomach, lungs, kidney and intestines was higher than plasma concentrations. Metabolite analysis of plasma, urine and feces samples demonstrated oxidized TTX, the only identified metabolite. In conclusion, TTX was rapidly absorbed and excreted in rats, a standard preclinical model used to guide the design of clinical trials. View Full-Text
Keywords: tetrodotoxin; ADME; TTX; 11-[3H]TTX; non-clinical pharmacokinetics tetrodotoxin; ADME; TTX; 11-[3H]TTX; non-clinical pharmacokinetics
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MDPI and ACS Style

Hong, B.; Chen, H.; Han, J.; Xie, Q.; He, J.; Bai, K.; Dong, Y.; Yi, R. A Study of 11-[3H]-Tetrodotoxin Absorption, Distribution, Metabolism and Excretion (ADME) in Adult Sprague-Dawley Rats. Mar. Drugs 2017, 15, 159.

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