Giuseppe
Emeritus
[Source: Antimicrobial Agents and Chemotherapy, full text: (LINK). Abstract, edited.]
------
Pharmacokinetics of zanamivir following intravenous administration to subjects with and without renal impairment
Stephen Weller 1#, Lori S. Jones 1, Yu Lou 1, Amanda Peppercorn 1 and Judith Ng-Cashin 1
Author Affiliations: <SUP>1</SUP>GlaxoSmithKline, Research Triangle Park, North Carolina
ABSTRACT
Intravenous zanamivir is in clinical development for the treatment of influenza in hospitalized patients many of whom have renal impairment. This open-label study evaluated zanamivir pharmacokinetics and clinical safety following a single 100mg intravenous infusion dose in subjects with impaired renal function compared with normal renal function. Male and female subjects between 18 and 79 years of age were recruited, four subjects to each renal function group (normal, mild, moderate, severe). Serial blood samples were collected up to 24 hours after dose administration (48 hours for severe renal impairment group) to estimate zanamivir serum pharmacokinetic parameters. Urine was collected over the same 24-hour (or 48-hour) period for estimation of renal clearance (CLr). Zanamivir pharmacokinetics were assessed by regression analysis of systemic clearance (CL) and CLr as a function of creatinine clearance (CLcr). Safety evaluations included adverse event monitoring, vital signs, electrocardiogram and clinical laboratory assessments. Zanamivir clearance (total and renal) significantly decreased with decreasing renal function, with corresponding increases in area under the concentration-time curve and elimination half-life. Renal impairment had no apparent effects on peak concentration or volume of distribution. Regression analysis indicated that zanamivir clearance was highly correlated (r<SUP>2</SUP>=0.89) with creatinine clearance: CL ≅ 7.08 + 0.826?CLcr. There were no patterns or trends in adverse events and no new safety concerns were identified following administration of intravenous zanamivir. Results from this study support the inclusion of subjects with renal impairment, with appropriate dose adjustment, in studies to evaluate intravenous zanamivir in the treatment of influenza.
FOOTNOTES
# Corresponding Author: steve.2.weller@gsk.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Stephen Weller 1#, Lori S. Jones 1, Yu Lou 1, Amanda Peppercorn 1 and Judith Ng-Cashin 1
Author Affiliations: <SUP>1</SUP>GlaxoSmithKline, Research Triangle Park, North Carolina
ABSTRACT
Intravenous zanamivir is in clinical development for the treatment of influenza in hospitalized patients many of whom have renal impairment. This open-label study evaluated zanamivir pharmacokinetics and clinical safety following a single 100mg intravenous infusion dose in subjects with impaired renal function compared with normal renal function. Male and female subjects between 18 and 79 years of age were recruited, four subjects to each renal function group (normal, mild, moderate, severe). Serial blood samples were collected up to 24 hours after dose administration (48 hours for severe renal impairment group) to estimate zanamivir serum pharmacokinetic parameters. Urine was collected over the same 24-hour (or 48-hour) period for estimation of renal clearance (CLr). Zanamivir pharmacokinetics were assessed by regression analysis of systemic clearance (CL) and CLr as a function of creatinine clearance (CLcr). Safety evaluations included adverse event monitoring, vital signs, electrocardiogram and clinical laboratory assessments. Zanamivir clearance (total and renal) significantly decreased with decreasing renal function, with corresponding increases in area under the concentration-time curve and elimination half-life. Renal impairment had no apparent effects on peak concentration or volume of distribution. Regression analysis indicated that zanamivir clearance was highly correlated (r<SUP>2</SUP>=0.89) with creatinine clearance: CL ≅ 7.08 + 0.826?CLcr. There were no patterns or trends in adverse events and no new safety concerns were identified following administration of intravenous zanamivir. Results from this study support the inclusion of subjects with renal impairment, with appropriate dose adjustment, in studies to evaluate intravenous zanamivir in the treatment of influenza.
FOOTNOTES
# Corresponding Author: steve.2.weller@gsk.com
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
------