title: Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.
abstract: Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.
authors.affiliation: Plastic Surgery and Burns, Hospital das Clinicas, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: David S
authors.initials: DS
authors.lastname: Gomez
authors.affiliation: Department of Pharmacy, Universidade Federal de São João del Rei, Divinópolis, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sanches-Giraud
authors.affiliation: School of Pharmaceutical Sciences University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Carlindo V
authors.initials: CV
authors.lastname: Silva
authors.affiliation: Plastic Surgery and Burns, Hospital das Clinicas, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Amanda M Ribas Rosa
authors.initials: AM
authors.lastname: Oliveira
authors.affiliation: Plastic Surgery and Burns, Hospital das Clinicas, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Joao Manoel
authors.initials: JM
authors.lastname: da Silva
authors.affiliation: Plastic Surgery and Burns, Hospital das Clinicas, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Rolf
authors.initials: R
authors.lastname: Gemperli
authors.affiliation: School of Pharmaceutical Sciences University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Silvia R C J
authors.initials: SR
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem