Flushing symptoms limit the use of
niacin as an effective treatment for
dyslipidemia;
laropiprant, a
prostaglandin D2 receptor subtype 1 antagonist, reduces
niacin-induced
flushing and is being developed in combination with
niacin. The aims of this study were to both determine the effect of
renal insufficiency on plasma pharmacokinetics of
laropiprant and to assess safety and tolerability in patients with severe
renal insufficiency. This open-label study compared the pharmacokinetics of a single
laropiprant 40-mg dose in 8 nondialyzed, severe
renal insufficiency patients (RIs) with healthy matched subjects (HSs) (24-hour
creatinine clearance <30 mL/min/1.73 m(2) and >80 mL/min/1.73 m(2) for RIs and HSs, respectively). In RIs,
laropiprant was well tolerated and the area under the concentration time curve (AUC(0-infinity)) was modestly higher (ratio of geometric least-squares means [GMR] for RIs to HSs was 1.58; 90% confidence interval [CI], 1.06-2.35); neither the maximum
laropiprant plasma concentration (C(max)) nor the time to C(max) (T(max)) was significantly affected. The apparent terminal half-life (t(1/2)) was 26.0 and 14.8 hours for RIs and HSs, respectively (P = 0.007). Similarly, for the inactive
laropiprant glucuronide metabolite, the GMR for AUC(0-infinity) was 2.17 (90% CI, 1.44-3.27), and the apparent t(1/2) values were 25.3 to 14.5 hours (P = 0.037) in RIs and HSs, respectively.
Renal insufficiency had no clinically significant effect on
laropiprant pharmacokinetics. Because
niacin and its metabolites are excreted through the kidneys, the combination of
niacin with
laropiprant should be used with caution in patients with renal impairment.