Chloramphenicol Pharmacokinetics in African children with severe malaria

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dc.creatorKokwaro, G.
dc.creatorMuchohi, Simon N.
dc.creatorOgutu, Benhards R.
dc.creatorNewton, Charles RJC
dc.date03/11/2015
dc.dateWed, 11 Mar 2015
dc.dateWed, 11 Mar 2015 19:01:50
dc.dateMonth: 8 Day: 26 Year: 2005
dc.dateWed, 11 Mar 2015 19:01:50
dc.date.accessioned2015-03-18T11:29:17Z
dc.date.available2015-03-18T11:29:17Z
dc.descriptionArticle published in Journal of tropical pediatrics
dc.descriptionThe objective of this study was to determine if the current dosage regimen for chloramphenicol (CAP) administered to children with severe malaria (SM) for presumptive treatment of concomitant bacterial meningitis achieves steady state plasma CAP concentrations within the reported therapeutic range of 10–25 mg/l. Fifteen children (11 male, 4 female) with a median age of 45 months (range: 10–108 months) and having SM, were administered multiple intravenous doses (25 mg/kg, 6 hourly for 72 h) of chloramphenicol sodium succinate (CAPS) for presumptive treatment of concomitant bacterial meningitis. Blood samples were collected over 72 h, and plasma CAPS, CAP and CSF CAP concentrations determined by high performance liquid chromatography. Average steady state CAP concentrations were approximately 17 mg/l, while mean fraction unbound (0.49) and CSF/plasma concentration ratio (0.65) were comparable to previously reported values in Caucasian children. Clearance was variable (mean^4.3 l/h), and trough plasma concentrations during the first dosing interval were approximately 6 mg/l. Simulations indicated that an initial of loading dose of 40 mg/kg CAPS, followed by a maintenance dose of 25 mg/kg every 6 h would result in trough CAP concentrations of approximately 10 mg/l and peak concentrations _25 mg/l throughout the treatment period. The current dosage regimen for CAP needs to include a loading dose of 40 mg/kg CAPS to rapidly achieve plasma CAP concentrations within the reported therapeutic range.
dc.description.abstract
dc.description.abstractThe objective of this study was to determine if the current dosage regimen for chloramphenicol (CAP) administered to children with severe malaria (SM) for presumptive treatment of concomitant bacterial meningitis achieves steady state plasma CAP concentrations within the reported therapeutic range of 10–25 mg/l. Fifteen children (11 male, 4 female) with a median age of 45 months (range: 10–108 months) and having SM, were administered multiple intravenous doses (25 mg/kg, 6 hourly for 72 h) of chloramphenicol sodium succinate (CAPS) for presumptive treatment of concomitant bacterial meningitis. Blood samples were collected over 72 h, and plasma CAPS, CAP and CSF CAP concentrations determined by high performance liquid chromatography. Average steady state CAP concentrations were approximately 17 mg/l, while mean fraction unbound (0.49) and CSF/plasma concentration ratio (0.65) were comparable to previously reported values in Caucasian children. Clearance was variable (mean=4.3 l/h), and trough plasma concentrations during the first dosing interval were approximately 6 mg/l. Simulations indicated that an initial of loading dose of 40 mg/kg CAPS, followed by a maintenance dose of 25 mg/kg every 6 h would result in trough CAP concentrations of approximately 10 mg/l and peak concentrations <25 mg/l throughout the treatment period. The current dosage regimen for CAP needs to include a loading dose of 40 mg/kg CAPS to rapidly achieve plasma CAP concentrations within the reported therapeutic range.
dc.formatIssue No.:4
dc.formatVolume Number:52
dc.formatPages:239 - 243
dc.identifier10.1093/tropej/fmi082
dc.identifier
dc.identifier.urihttp://hdl.handle.net/11071/3857
dc.languageeng
dc.publisherJournal of tropical pediatrics
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dc.subjectMalaria
dc.subjectHealth
dc.subjectAfrica
dc.subjectChloramphenicol Pharmacokinetics
dc.titleChloramphenicol Pharmacokinetics in African children with severe malaria
dc.typeArticle
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