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The pharmacokinetics of PF-734200, a DPP-IV inhibitor, in subjects with renal insufficiency.
- Source :
-
British Journal of Clinical Pharmacology . Jul2011, Vol. 72 Issue 1, p85-91. 7p. 3 Charts, 3 Graphs. - Publication Year :
- 2011
-
Abstract
- • Data demonstrating the pharmacokinetics (PK), efficacy and tolerability of PF-734200, a potent DPP-IV inhibitor in subjects with normal renal function, have been published or presented. • This study provides better data on the PK of PF-734200 in subjects with varying degrees of renal insufficiency and in subjects with end-stage renal disease undergoing haemodialysis. In assessing the effects of renal impairment on the PK of PF-734200, this study provides evidence for potential dose adjustment of PF-734200 in patients with certain categories of renal impairment. PF-734200 is a potent, selective inhibitor of DPP-IV. This two-part study evaluated the pharmacokinetics (PK) of oral 20 mg PF-734200 in subjects with varying degrees of renal insufficiency or with end-stage renal disease (ESRD) requiring chronic haemodialysis (HD). The study also assessed the HD clearance of PF-734200 in ESRD. Part 1 included subjects with normal renal function or renal insufficiency but not on HD. Subjects received a single dose of 20 mg PF-734200 while fasting and serum and urine samples were collected. In part 2, period 1, 1 h after HD, a single 20-mg dose was given to subjects with ESRD and serum samples were collected. After a 7-day washout, subjects received another dose followed by collection of serum samples (period 2), during which HD was initiated 4 h after dosing. Dialysate samples were collected to quantify amount of drug removed, from which HD clearance was calculated. The fraction of drug dialysed was calculated using an AUC-based method. Systemic exposures of PF-734200 increased approximately 1.5-, 2.2-, 2.1- and 2.8-fold in subjects with mild, moderate, or severe renal insufficiency or ESRD, respectively, compared with subjects with normal renal function. The terminal half-life increased from 16.2 h in subjects with normal renal function to 36.6 h in subjects with ESRD. Approximately, 29% of PF-734200 in the body after a single-dose administration was dialysed by 4 h HD. Systemic exposure of PF-734200 increases with decreasing renal function. The effect of HD on drug removal is modest. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03065251
- Volume :
- 72
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- British Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 61140466
- Full Text :
- https://doi.org/10.1111/j.1365-2125.2011.03954.x