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Sökning: onr:"swepub:oai:DiVA.org:uu-113826" > Population pharmaco...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003607naa a2200409 4500
001oai:DiVA.org:uu-113826
003SwePub
008100204s2009 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1138262 URI
0247 a https://doi.org/10.1128/AAC.01361-082 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Plachouras, D4 aut
2451 0a Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria
264 1c 2009
338 a print2 rdacarrier
520 a Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.
653 a MEDICINE
653 a MEDICIN
7001 a Karvanen, Mu Uppsala universitet,Infektionssjukdomar4 aut
7001 a Friberg, L. E.u Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri4 aut0 (Swepub:uu)lenasimo
7001 a Papadomichelakis, E4 aut
7001 a Antoniadou, A4 aut
7001 a Tsangaris, I4 aut
7001 a Karaiskos, I4 aut
7001 a Poulakou, G4 aut
7001 a Kontopidou, F4 aut
7001 a Armaganidis, A4 aut
7001 a Cars, Ou Uppsala universitet,Infektionssjukdomar4 aut
7001 a Giamarellou, H4 aut
7102 a Uppsala universitetb Infektionssjukdomar4 org
7730 t Antimicrobial Agents and Chemotherapyg 53:8, s. 3430-3436q 53:8<3430-3436x 0066-4804x 1098-6596
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-113826
8564 8u https://doi.org/10.1128/AAC.01361-08

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