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Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Antimicrobial Agents and Chemotherapy, 62, 2018, 6 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| author_facet |
Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. |
|---|---|
| author |
Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. |
| spellingShingle |
Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. Antimicrobial Agents and Chemotherapy Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients Infectious Diseases Pharmacology (medical) Pharmacology |
| author_sort |
sime, fekade b. |
| spelling |
Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.00242-18 <jats:title>ABSTRACT</jats:title> <jats:p> To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period ( <jats:italic>C</jats:italic> <jats:sub>max</jats:sub> ), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC <jats:sub>0–∞</jats:sub> ), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution ( <jats:italic>V</jats:italic> ), 529.1 liters (352.2 to 720.6 liters). The <jats:italic>V</jats:italic> and CL were greater than 2-fold and the AUC <jats:sub>0–∞</jats:sub> was 39% of the values reported for heathy volunteers. The AUC <jats:sub>0–∞</jats:sub> was only 52% of the steady-state AUC <jats:sub>0–24</jats:sub> reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients. </jats:p> Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients Antimicrobial Agents and Chemotherapy |
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| title |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_unstemmed |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_full |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_fullStr |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_full_unstemmed |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_short |
Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_sort |
pharmacokinetics of intravenous posaconazole in critically ill patients |
| topic |
Infectious Diseases Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1128/aac.00242-18 |
| publishDate |
2018 |
| physical |
|
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>
To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period (
<jats:italic>C</jats:italic>
<jats:sub>max</jats:sub>
), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC
<jats:sub>0–∞</jats:sub>
), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution (
<jats:italic>V</jats:italic>
), 529.1 liters (352.2 to 720.6 liters). The
<jats:italic>V</jats:italic>
and CL were greater than 2-fold and the AUC
<jats:sub>0–∞</jats:sub>
was 39% of the values reported for heathy volunteers. The AUC
<jats:sub>0–∞</jats:sub>
was only 52% of the steady-state AUC
<jats:sub>0–24</jats:sub>
reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients.
</jats:p> |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period ( <jats:italic>C</jats:italic> <jats:sub>max</jats:sub> ), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC <jats:sub>0–∞</jats:sub> ), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution ( <jats:italic>V</jats:italic> ), 529.1 liters (352.2 to 720.6 liters). The <jats:italic>V</jats:italic> and CL were greater than 2-fold and the AUC <jats:sub>0–∞</jats:sub> was 39% of the values reported for heathy volunteers. The AUC <jats:sub>0–∞</jats:sub> was only 52% of the steady-state AUC <jats:sub>0–24</jats:sub> reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients. </jats:p> |
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| spelling | Sime, Fekade B. Stuart, Janine Butler, Jenie Starr, Therese Wallis, Steven C. Pandey, Saurabh Lipman, Jeffrey Roberts, Jason A. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.00242-18 <jats:title>ABSTRACT</jats:title> <jats:p> To date, there is no information on the intravenous (i.v.) posaconazole pharmacokinetics for intensive care unit (ICU) patients. This prospective observational study aimed to describe the pharmacokinetics of a single dose of i.v. posaconazole in critically ill patients. Patients with no history of allergy to triazole antifungals and requiring systemic antifungal therapy were enrolled if they were aged ≥18 years, central venous access was available, they were not pregnant, and they had not received prior posaconazole or drugs interacting with posaconazole. A single dose of 300 mg posaconazole was administered over 90 min. Total plasma concentrations were measured from serial plasma samples collected over 48 h, using a validated chromatographic method. The pharmacokinetic data set was analyzed by noncompartmental methods. Eight patients (7 male) were enrolled with the following characteristics: median age, 46 years (interquartile range [IQR], 40 to 51 years); median weight, 68 kg (IQR, 65 to 82 kg); and median albumin concentration, 20 g/liter (IQR, 18 to 24 g/liter). Median (IQR) pharmacokinetic parameter estimates were as follows: observed maximum concentration during sampling period ( <jats:italic>C</jats:italic> <jats:sub>max</jats:sub> ), 1,702 ng/ml (1,352 to 2,141 ng/ml); area under the concentration-time curve from zero to infinity (AUC <jats:sub>0–∞</jats:sub> ), 17,932 ng · h/ml (13,823 to 27,905 ng · h/ml); clearance (CL), 16.8 liters/h (11.1 to 21.7 liters/h); and volume of distribution ( <jats:italic>V</jats:italic> ), 529.1 liters (352.2 to 720.6 liters). The <jats:italic>V</jats:italic> and CL were greater than 2-fold and the AUC <jats:sub>0–∞</jats:sub> was 39% of the values reported for heathy volunteers. The AUC <jats:sub>0–∞</jats:sub> was only 52% of the steady-state AUC <jats:sub>0–24</jats:sub> reported for hematology patients. The median of estimated average steady-state concentrations was 747 ng/ml (IQR, 576 to 1,163 ng/ml), which is within but close to the lower end of the previously recommended therapeutic range of 500 to 2,500 ng/ml. In conclusion, we observed different pharmacokinetics of i.v. posaconazole in this cohort of critically ill patients compared to those in healthy volunteers and hematology patients. </jats:p> Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients Antimicrobial Agents and Chemotherapy |
| spellingShingle | Sime, Fekade B., Stuart, Janine, Butler, Jenie, Starr, Therese, Wallis, Steven C., Pandey, Saurabh, Lipman, Jeffrey, Roberts, Jason A., Antimicrobial Agents and Chemotherapy, Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients, Infectious Diseases, Pharmacology (medical), Pharmacology |
| title | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_full | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_fullStr | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_full_unstemmed | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_short | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| title_sort | pharmacokinetics of intravenous posaconazole in critically ill patients |
| title_unstemmed | Pharmacokinetics of Intravenous Posaconazole in Critically Ill Patients |
| topic | Infectious Diseases, Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1128/aac.00242-18 |