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Sökning: onr:"swepub:oai:DiVA.org:uu-184479" > Application of a Lo...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003542naa a2200385 4500
001oai:DiVA.org:uu-184479
003SwePub
008121107s2012 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1844792 URI
0247 a https://doi.org/10.1128/AAC.06426-112 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Mohamed, Ami Fazlin Syedu Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri4 aut0 (Swepub:uu)amisy435
2451 0a Application of a Loading Dose of Colistin Methanesulfonate in Critically Ill Patients :b Population Pharmacokinetics, Protein Binding, and Prediction of Bacterial Kill
264 1c 2012
338 a print2 rdacarrier
520 a A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.
7001 a Karaiskos, Ilias4 aut
7001 a Plachouras, Diamantis4 aut
7001 a Karvanen, Mattiu Uppsala universitet,Infektionssjukdomar4 aut0 (Swepub:uu)matka637
7001 a Pontikis, Konstantinos4 aut
7001 a Jansson, Britt4 aut
7001 a Papadomichelakis, Evangelos4 aut
7001 a Antoniadou, Anastasia4 aut
7001 a Giamarellou, Helen4 aut
7001 a Armaganidis, Apostolos4 aut
7001 a Cars, Ottou Uppsala universitet,Infektionssjukdomar4 aut0 (Swepub:uu)ottocars
7001 a Friberg, Lena E.u Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri4 aut0 (Swepub:uu)lenasimo
7102 a Uppsala universitetb Institutionen för farmaceutisk biovetenskap4 org
7730 t Antimicrobial Agents and Chemotherapyg 56:8, s. 4241-4249q 56:8<4241-4249x 0066-4804x 1098-6596
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-184479
8564 8u https://doi.org/10.1128/AAC.06426-11

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