کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597218 1132573 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Toxicology and pharmacokinetics of piperaquine in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Toxicology and pharmacokinetics of piperaquine in mice
چکیده انگلیسی

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 100 mg/(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: t½, 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 249, Issue 1, 10 July 2008, Pages 55–61
نویسندگان
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