Imipenem pharmacokinetics in patients with burns

Bradley Boucher, William Hickerson, David A. Kuhl, Anne Marie Bombassaro, George S. Jaresko

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of BPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p > 0.05). Combined mean (± SD) parameter estimates for the two dosing periods were as follows: Vc, 0.11 ± 0.06 L/kg; Vss, 0.22 ± 0.06 L/kg; CL, 12.5 ± 3.6 L/hr/1.73 m2; t 1 2α, 0.18 ± 0.13 hr; t 1 2β 1.12 ± 0.44 hr. Mean clearance in two patients with creatinine clearance values >150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p > 0.05). Creatinine clearance ranged from 17 to 218 ml/min/ 1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.0001). No significant association was found between total body surface area burns and imipenem clearance (p > 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists. Measured creatinine clearance values may be useful in estimating imipenem clearance clinically.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume48
Issue number2
DOIs
StatePublished - Jan 1 1990

Fingerprint

Imipenem
Burns
Pharmacokinetics
Creatinine
Healthy Volunteers
Urine Specimen Collection
Body Surface Area

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Imipenem pharmacokinetics in patients with burns. / Boucher, Bradley; Hickerson, William; Kuhl, David A.; Bombassaro, Anne Marie; Jaresko, George S.

In: Clinical Pharmacology and Therapeutics, Vol. 48, No. 2, 01.01.1990, p. 130-137.

Research output: Contribution to journalArticle

Boucher, Bradley ; Hickerson, William ; Kuhl, David A. ; Bombassaro, Anne Marie ; Jaresko, George S. / Imipenem pharmacokinetics in patients with burns. In: Clinical Pharmacology and Therapeutics. 1990 ; Vol. 48, No. 2. pp. 130-137.
@article{e6a846d19cb74fa1ba9f7f84d28ba45b,
title = "Imipenem pharmacokinetics in patients with burns",
abstract = "The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of BPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p > 0.05). Combined mean (± SD) parameter estimates for the two dosing periods were as follows: Vc, 0.11 ± 0.06 L/kg; Vss, 0.22 ± 0.06 L/kg; CL, 12.5 ± 3.6 L/hr/1.73 m2; t 1 2α, 0.18 ± 0.13 hr; t 1 2β 1.12 ± 0.44 hr. Mean clearance in two patients with creatinine clearance values >150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p > 0.05). Creatinine clearance ranged from 17 to 218 ml/min/ 1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.0001). No significant association was found between total body surface area burns and imipenem clearance (p > 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists. Measured creatinine clearance values may be useful in estimating imipenem clearance clinically.",
author = "Bradley Boucher and William Hickerson and Kuhl, {David A.} and Bombassaro, {Anne Marie} and Jaresko, {George S.}",
year = "1990",
month = "1",
day = "1",
doi = "10.1038/clpt.1990.127",
language = "English (US)",
volume = "48",
pages = "130--137",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Imipenem pharmacokinetics in patients with burns

AU - Boucher, Bradley

AU - Hickerson, William

AU - Kuhl, David A.

AU - Bombassaro, Anne Marie

AU - Jaresko, George S.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of BPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p > 0.05). Combined mean (± SD) parameter estimates for the two dosing periods were as follows: Vc, 0.11 ± 0.06 L/kg; Vss, 0.22 ± 0.06 L/kg; CL, 12.5 ± 3.6 L/hr/1.73 m2; t 1 2α, 0.18 ± 0.13 hr; t 1 2β 1.12 ± 0.44 hr. Mean clearance in two patients with creatinine clearance values >150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p > 0.05). Creatinine clearance ranged from 17 to 218 ml/min/ 1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.0001). No significant association was found between total body surface area burns and imipenem clearance (p > 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists. Measured creatinine clearance values may be useful in estimating imipenem clearance clinically.

AB - The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of BPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p > 0.05). Combined mean (± SD) parameter estimates for the two dosing periods were as follows: Vc, 0.11 ± 0.06 L/kg; Vss, 0.22 ± 0.06 L/kg; CL, 12.5 ± 3.6 L/hr/1.73 m2; t 1 2α, 0.18 ± 0.13 hr; t 1 2β 1.12 ± 0.44 hr. Mean clearance in two patients with creatinine clearance values >150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p > 0.05). Creatinine clearance ranged from 17 to 218 ml/min/ 1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.0001). No significant association was found between total body surface area burns and imipenem clearance (p > 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists. Measured creatinine clearance values may be useful in estimating imipenem clearance clinically.

UR - http://www.scopus.com/inward/record.url?scp=0025183524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025183524&partnerID=8YFLogxK

U2 - 10.1038/clpt.1990.127

DO - 10.1038/clpt.1990.127

M3 - Article

C2 - 2379384

AN - SCOPUS:0025183524

VL - 48

SP - 130

EP - 137

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 2

ER -