Repeated‐Dose Toxicity Studies in Nonclinical Drug Development

Azri-Meehan, Shana; Latriano, Louise

doi:10.1002/9781118517000.ch12

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Cited by 2 publications

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Use of toxicokinetic data in preclinical safety assessment

Kaur,

Tekade,

Vasdev

et al. 2024

Public Health and Toxicology Issues Drug Research, Volume 2

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Use of toxicokinetic data in preclinical safety assessment

Kaur,

Tekade,

Vasdev

et al. 2024

Public Health and Toxicology Issues Drug Research, Volume 2

View full text Add to dashboard Cite

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

Cunha-Júnior

Martins

Canto‐Cavalheiro

et al. 2016

Antimicrob Agents Chemother

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e Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and antileukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg/kg of body weight/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An in vivo toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.

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Repeated‐Dose Toxicity Studies in Nonclinical Drug Development

Cited by 2 publications

References 22 publications

Use of toxicokinetic data in preclinical safety assessment

Use of toxicokinetic data in preclinical safety assessment

Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis

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