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

Hong, Bihong; Hui, Chi Man; Han, Jiacai; Xie, Quanling; He, Jianlin; Bai, Kaikai; Dong, Yanming; Yi, Ruizao

doi:10.3390/md15060159

Cited by 18 publications

(44 citation statements)

References 29 publications

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“…administration. Meanwhile, TTX has also been shown to be rapidly distributed in the gastrointestinal tract after entering the body [ 20 ], suggesting that sodium channels in the gastrointestinal tract are blocked, which likely prolonged the duration of TTX absorption. This may be related to the long-term efficacy of oral administration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

et al. 2018

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Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (Cmax) at around 2 h, with an elimination half-life time (t1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD50) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection.

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Section: Discussionmentioning

confidence: 99%

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

et al. 2018

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“…On the other hand, metabolite analysis of plasma, urine and feces samples demonstrated the presence of only oxidized TTX. As a conclusion, TTX was found to be rapidly absorbed and excreted in rats [62].…”

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

Public Health Risks Associated with Tetrodotoxin and Its Analogues in European Waters: Recent Advances after The EFSA Scientific Opinion

Katikou

2019

Toxins

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Tetrodotoxin (TTX) and its analogues are naturally occurring toxins responsible worldwide for human intoxication cases and fatalities, mainly associated with pufferfish consumption. In the last decade, TTXs were detected in marine bivalves and gastropods from European waters. As TTXs are not regulated or monitored at EU level, their unexpected occurrence in shellfish raised concerns as a food safety hazard and revealed the necessity of a thorough assessment on the public health risks associated with their presence. For this reason, the European Food Safety Authority (EFSA) was requested by the European Commission to provide a scientific opinion, finally adopted in March 2017, according to which a provisional concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. The EFSA expert panel, however, recognized a number of shortcomings and uncertainties related to the unavailability of sufficient scientific data and provided relevant recommendations for future research to overcome these data gaps identified in order to further refine the risk assessment on TTXs. The present review aims to summarize the knowledge obtained towards addressing these recommendations in the two years following publication of the EFSA opinion, at the same time highlighting the points requiring further investigation.

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“…administration (4.12 ng/mL). The value of V d was 192,752.13 ± 46,492.16 mL/kg, suggesting a low plasma concentrations of TTX, and TTX might mainly distributed in tissue or be confined in a certain organ, properly in intestine according to our previous study [5]. Compared with the results of i.v.…”

Section: Studies Of Intravenous (Iv) Ttx Administrationmentioning

confidence: 62%

“…Further, the half-life (t 1/2 ) of TTX is short, and the effective blood concentration can only be maintained for about 2 h after i.m. injection [5]. In order to maintain the efficacy, frequent i.m.…”

Section: Introductionmentioning

confidence: 99%

Analgesia Effect of Enteric Sustained-Release Tetrodotoxin Pellets in the Rat

Hong

Sun

et al. 2020

Pharmaceutics

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Tetrodotoxin (TTX) was identified as a latent neurotoxin that has a significant analgesia effect. It was rapidly absorbed and excreted in rat after intramuscular (i.m.) injection. To maintain the effect, frequent injections were required. The enteric sustained-release TTX pellets with sucrose pellets as a drug carrier was prepared by fluidized bed spray irrigation, coated in sequence with Eudragit NE30D as a sustained-release layer, hydroxypropyl methylcellulose (HPMC) as a barrier layer and Eudragit L30D-55 as an enteric coating. TTX in the pellets could be sustained released for 12 h in dissolution test. In vivo, TTX pellets reached Cmax at 5 h, and t1/2 was 14.52 ± 2.37 h after intragastrically (i.g.) administration in rat. In acetic acid induced writhing test in rat, the pellets at the dosages of 20, 40, 60 and 80 μg·kg−1 produced analgesic effect at about 1.5 h to 9 h and the strongest effect was at about 3 h to 6 h. Simultaneously, the LD50 of the enteric sustained-release TTX pellets was 840.13 μg·kg−1, and the ED50 was about 30 μg·kg−1. Thus, the therapeutic index was about 25. The enteric sustained-release TTX pellets with absolute analgesia effect and greatly enhanced safety was prepared.

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

Cited by 18 publications

References 29 publications

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia

Public Health Risks Associated with Tetrodotoxin and Its Analogues in European Waters: Recent Advances after The EFSA Scientific Opinion

Analgesia Effect of Enteric Sustained-Release Tetrodotoxin Pellets in the Rat

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