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Browsing by Author "S. Sandberg"

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    Pharmacokinetics and metabolism of the antimalarial piperaquine after intravenous and oral single doses to the rat
    (2008-01-01) J. Tarning; N. Lindegardh; S. Sandberg; N. J.P. Day; N. J. White; M. Ashton; Goteborg University, Sahlgrenska Academy; Mahidol University; Churchill Hospital
    This study aimed to evaluate the pharmacokinetic properties of pipera-quine in the rat after intravenous and oral administration, and to identify and characterize the main piperaquine metabolites in rat plasma, urine, faeces and bile after intravenous administration. Male Sprague - Dawley rats were administered piperaquine as an emulsion orally or as a short-term intravenous infusion. Venous blood for pharmacokinetic evaluation was frequently withdrawn up to 90 h after dose. Urine, bile and faeces were collected after an infusion in rats kept in metabolic cages or in anesthetized rats. Pharmacokinetic characterization was done by compartmental modeling and non-compartmental analysis using WinNonlin. Piperaquine disposition was best described by a 3-compartment model with a rapid initial distribution phase after intravenous administration. The pharmacokinetics of piperaquine was characterized by a low clearance, a large volume of distribution and a long terminal half-life. Piperaquine displayed a low biliary clearance and less than 1% of the total dose was recovered in urine. The absolute oral bioavailability was approximately 50%. The main metabolite after intravenous administration of piperaquine was a carboxylic acid product identical to that reported in humans. The similarity with results in humans indicates the rat to be a suitable species for nonclinical in vivo piperaquine studies. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

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