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• W2034591842 abstract "Pharmacokinetic and toxicological data for piperaquine (PQ) - a bisquinoline antimalarial drug - are limited, despite strong evidence of clinical efficacy. Our aim was to conduct a detailed toxicological investigation of PQ in Swiss mice. The study comprised three phases: (i) oral PQ phosphate (PQP) at doses ranging from 0 to 600 mg/(kg day) for 5 days. Pathology tests included haematological and biochemical indices, and histopathology of the liver, heart and kidneys. (ii) PQP doses of 0-300 mg/(kg day) for 12 days and pathology tests as described. (iii) Pharmacokinetic parameters determined from mice given 100mg/(kg day) PQP for 5 days. Blood was harvested from mice over 56 days and plasma analysed by HPLC. Mice given low doses of PQ had stable, normal body and organ weights. Weight loss was observed in mice given high doses and was accompanied by increased liver and kidney weights. Principal haematological effects were modest fluctuations in total white cells and neutrophils; biochemical effects were elevated ALT and low albumin in high-dose groups. Liver histopathology revealed minor cytoplasmic and inflammatory effects. PQ treatment did not affect heart muscle but minor renal changes were observed at high doses. Pharmacokinetic parameters were consistent with previous studies: t1/2, CL and V were 16 days, 1.36 L/(h kg) and 756 L/kg, respectively. PQ may cause minor hepatotoxicity and renal tubular cell damage, and adversely affect selected haematological indices, as demonstrated at cumulative doses approximately 50 times those recommended in humans. Significant effects in humans will likely be infrequent and dose-related." @default.
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• W2034591842 date "2008-07-01" @default.
• W2034591842 modified "2023-10-17" @default.
• W2034591842 title "Toxicology and pharmacokinetics of piperaquine in mice" @default.
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• W2034591842 doi "https://doi.org/10.1016/j.tox.2008.04.004" @default.
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