Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: A randomized crossover clinical trial

Erik S. Barquist, Eleanor Gomez-Fein, Ernest F J Block, Gary Collin, Heythem Alzamel, Octavio V. Martinez

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BACKGROUND: Patients with nonapposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. METHODS: Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. RESULTS: Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% ± 30% in the open abdomen and 63% ± 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. CONCLUSION: The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.

Original languageEnglish
Pages (from-to)159-163
Number of pages5
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume63
Issue number1
DOIs
StatePublished - Jul 1 2007

Fingerprint

Fluconazole
Abdominal Wall
Critical Illness
Cross-Over Studies
Biological Availability
Randomized Controlled Trials
Wounds and Injuries
Abdomen
Small Intestine
Injury Severity Score
Candida
Intravenous Administration
Laparotomy
Fungi

Keywords

  • Bioavailability
  • Critical illness
  • Fluconazole
  • Laparostomy
  • Open abdomen
  • Pharmacokinetics
  • Surgery complications

ASJC Scopus subject areas

  • Surgery

Cite this

Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure : A randomized crossover clinical trial. / Barquist, Erik S.; Gomez-Fein, Eleanor; Block, Ernest F J; Collin, Gary; Alzamel, Heythem; Martinez, Octavio V.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 63, No. 1, 01.07.2007, p. 159-163.

Research output: Contribution to journalArticle

@article{a0120ced60d641dfb4ae4b29bad7a3a5,
title = "Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: A randomized crossover clinical trial",
abstract = "BACKGROUND: Patients with nonapposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with {"}open abdomens{"} would have bioavailability similar to that of matched patients with closed fascial edges. METHODS: Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. RESULTS: Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51{\%} ± 30{\%} in the open abdomen and 63{\%} ± 19{\%} (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30{\%}-100{\%} in both groups. Three patients developed rectal colonization with Candida krusei. CONCLUSION: The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.",
keywords = "Bioavailability, Critical illness, Fluconazole, Laparostomy, Open abdomen, Pharmacokinetics, Surgery complications",
author = "Barquist, {Erik S.} and Eleanor Gomez-Fein and Block, {Ernest F J} and Gary Collin and Heythem Alzamel and Martinez, {Octavio V.}",
year = "2007",
month = "7",
day = "1",
doi = "10.1097/01.ta.0000232011.59630.93",
language = "English",
volume = "63",
pages = "159--163",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure

T2 - A randomized crossover clinical trial

AU - Barquist, Erik S.

AU - Gomez-Fein, Eleanor

AU - Block, Ernest F J

AU - Collin, Gary

AU - Alzamel, Heythem

AU - Martinez, Octavio V.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - BACKGROUND: Patients with nonapposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. METHODS: Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. RESULTS: Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% ± 30% in the open abdomen and 63% ± 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. CONCLUSION: The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.

AB - BACKGROUND: Patients with nonapposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. METHODS: Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. RESULTS: Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% ± 30% in the open abdomen and 63% ± 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. CONCLUSION: The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.

KW - Bioavailability

KW - Critical illness

KW - Fluconazole

KW - Laparostomy

KW - Open abdomen

KW - Pharmacokinetics

KW - Surgery complications

UR - http://www.scopus.com/inward/record.url?scp=34447319700&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447319700&partnerID=8YFLogxK

U2 - 10.1097/01.ta.0000232011.59630.93

DO - 10.1097/01.ta.0000232011.59630.93

M3 - Article

C2 - 17622884

AN - SCOPUS:34447319700

VL - 63

SP - 159

EP - 163

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 1

ER -