Acute toxicity of oral pyronaridine in Sprague-Dawley rats

Aedah Abu Bakar¹, Sharif Mahsufi Mansor¹, Abas Hj. Husin², Piero Olliaro^1,3,V. Navaratnam¹

1. Centre for Drug Research, University Science Malaysia. 11800 Minden, Penang, Malaysia

2. Department of Pharmacology, School of Pharmaceutical Sciences, University Science Malaysia. 11800 Minden, Penang, Malaysia

3. UNDP/World Bank/WHO Special Programme on Research and Training in Tropical Diseases, CDS Cluster, 20, Avenue Appia CH-1211 Geneva, Switzerland

Correspondence: Dr Navaratnam V; email: This email address is being protected from spambots. You need JavaScript enabled to view it.

CITATION: Aedah Abu Bakar, Sharif Mahsufi Mansor, Abas Hj. Husin, Piero Olliaro, V. Navaratnam. Acute toxicity of oral pyronaridine in Sprague-Dawley rats. International Medical Research Journal. 2000;4(2):99–102. 

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ABSTRACT

Only partial information exists on the toxicology of pyronaridine, a synthetic antimalarial developed in China in the 1970-80's. The present study was designed to complement available data and obtain information on its toxic effects in fewer animals than that usually used to determine the value of the LD 50 (often judged marginally informative, toxicologically inadequate, and misleading, especially when derived from single-dose studies). The observations carried out included change in bodyweight, onset of mortality, overt toxicity signs and recovery, and gross pathological changes in target organs. Male rats were more susceptible than female rats to the toxic effect of pyronaridine (LD50 was 1491.93 ± 103.50 mg/kg for female and 1139.70 ± 110.30 for male rats). The LD₅₀ determined by the moving average method was similar to that determined by probit analysis. The mean time to death of female rats was dose-dependant. The acute toxicity signs observed in treated animals included decrease in spontaneous motor activities, somnolence, watery stools, catalepsy, tremor and convulsion. Animals that died developed tremor, then catalepsy followed by convulsion before death. The single administration of high dose ( 1000 mg/kg-2000 mg/kg) pyronaridine resulted in the shutdown of the central nervous system.

KEYWORDS: Pyronaridine, LD_50, moving average, probit analysis, central nervous system