Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease

R. Courtney, Angela Sansone, William Smith, T. Marbury, P. Statkevich, M. Martinho, M. Laughlin, S. Swan

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL CR, = 50-80 mL/ min), moderate (CLCR = 20-49 mL/min), and severe chronic renal disease (CLCR <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, Cmax, CL/F, and t 1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalJournal of Clinical Pharmacology
Volume45
Issue number2
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Chronic Renal Insufficiency
Pharmacokinetics
Safety
Renal Dialysis
Triazoles
Liver Function Tests
Protein Binding
posaconazole
Healthy Volunteers
Kidney

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease. / Courtney, R.; Sansone, Angela; Smith, William; Marbury, T.; Statkevich, P.; Martinho, M.; Laughlin, M.; Swan, S.

In: Journal of Clinical Pharmacology, Vol. 45, No. 2, 01.02.2005, p. 185-192.

Research output: Contribution to journalArticle

Courtney, R. ; Sansone, Angela ; Smith, William ; Marbury, T. ; Statkevich, P. ; Martinho, M. ; Laughlin, M. ; Swan, S. / Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease. In: Journal of Clinical Pharmacology. 2005 ; Vol. 45, No. 2. pp. 185-192.
@article{ab85b19dc9cd4fa4a4cc6392df50ad2f,
title = "Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease",
abstract = "Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL CR, = 50-80 mL/ min), moderate (CLCR = 20-49 mL/min), and severe chronic renal disease (CLCR <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, Cmax, CL/F, and t 1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3{\%}, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98{\%}) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.",
author = "R. Courtney and Angela Sansone and William Smith and T. Marbury and P. Statkevich and M. Martinho and M. Laughlin and S. Swan",
year = "2005",
month = "2",
day = "1",
doi = "10.1177/0091270004271402",
language = "English (US)",
volume = "45",
pages = "185--192",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease

AU - Courtney, R.

AU - Sansone, Angela

AU - Smith, William

AU - Marbury, T.

AU - Statkevich, P.

AU - Martinho, M.

AU - Laughlin, M.

AU - Swan, S.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL CR, = 50-80 mL/ min), moderate (CLCR = 20-49 mL/min), and severe chronic renal disease (CLCR <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, Cmax, CL/F, and t 1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

AB - Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL CR, = 50-80 mL/ min), moderate (CLCR = 20-49 mL/min), and severe chronic renal disease (CLCR <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, Cmax, CL/F, and t 1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

UR - http://www.scopus.com/inward/record.url?scp=16844387466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=16844387466&partnerID=8YFLogxK

U2 - 10.1177/0091270004271402

DO - 10.1177/0091270004271402

M3 - Article

C2 - 15647411

AN - SCOPUS:16844387466

VL - 45

SP - 185

EP - 192

JO - Journal of Clinical Pharmacology

JF - Journal of Clinical Pharmacology

SN - 0091-2700

IS - 2

ER -