Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Pharmacokinetics of laropiprant and glucuronide metabolite in patients with severe renal insufficiency. 1943 74

Laropiprant (LRPT), a prostaglandin D2 receptor 1 antagonist shown to reduce niacin-induced flushing symptoms, is being developed in combination with niacin for the treatment of dyslipidemia. This study assessed the pharmacokinetics/pharmacodynamics of single-dose warfarin in the presence/absence of multiple-dose LRPT. Thirteen subjects received 2 treatments in random order separated by > or =10-day washout: (1) multiple-dose LRPT 40 mg/d for 12 days (days -5 to 7) with coadministered single-dose warfarin 30 mg (day 6) and (2) single-dose warfarin 30 mg (day 1). R+- and S(-)-warfarin and international normalized ratio (INR) were assayed predose and up to 168 hours postdose. Comparability was declared if the 90% confidence intervals (CIs) for the geometric mean ratio (GMR; warfarin + LRPT/warfarin alone) of area under the plasma concentration curve from zero to infinity (AUC0-infinity) for R+- and S(-)-warfarin were contained within (0.80, 1.25). The estimated GMRs of AUC0-infinity (90% CIs) were 1.02 (0.96, 1.09) and 1.04 (0.98, 1.09) for R+- and S(-)-warfarin, respectively. The estimated GMRs of maximum plasma concentration (Cmax) (90% CIs) were 1.13 (1.02, 1.26) and 1.11 (0.99, 1.24) for R+- and S(-)-warfarin, respectively. The estimated GMRs of area under the prothrombin time INR curve from 0 to 168 hours on day 21 (INR AUC0-168 h) and average maximum observed prothrombin time INR (INRmax) were 1.02 (0.99, 1.05) and 1.04 (0.98, 1.10), respectively. There was no evidence of clinically meaningful alterations in the pharmacokinetics and pharmacodynamics (ie, INR) of R(+)- or S(-)-warfarin after coadministration of multiple-dose LRPT and single-dose warfarin.
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PMID:Influence of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, on the pharmacokinetics and pharmacodynamics of warfarin. 1945 60

There are many factors that increase the risk of cardiovascular disease, and a prominent factor among these is dyslipidemia. The following literature review focuses on the use of niacin therapy in order to treat dyslipidemia and how to control the associated "niacin flush." The associated studies gathered are reviews and randomized control trials. They were obtained by using electronic searches. Certain keywords took precedence, and articles focusing on niacin therapy were chosen. Recent research has found promising insight into more effective prevention of the niacin-mediated flush through a selective antagonist for the prostaglandin D2 receptor, laropiprant. Aspirin (or NSAIDs) also provide some prevention for flushing, although recent studies have shown that it is not as effective as laropiprant. There is a need for further research in order to come to a clear conclusion regarding combined therapies of aspirin and laropiprant pretreatment, as well as exact dosage requirements.
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PMID:Mechanisms of flushing due to niacin and abolition of these effects. 1987 84

Laropiprant is a prostaglandin D2 receptor 1 antagonist that is being developed in combination with niacin for the treatment of dyslipidemia. This randomized clinical study evaluated the effect of laropiprant on the pharmacokinetics of ethinyl estradiol (EE) and norelgestromin (NGMN), the principal circulating metabolite of norgestimate, in healthy women receiving 3 or more months of an oral contraceptive (Ortho Tri-Cyclen; Ortho-McNeil Pharmaceutical, Raritan, NJ), which contains EE and norgestimate. Twenty-one female subjects with normal menstrual cycles received the oral contraceptive on Days 1 to 21 during two consecutive contraceptive cycles. Subjects received double-blind 40 mg/day laropiprant or placebo on Days 1 to 21 of each contraceptive cycle. Plasma samples were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose on Day 21 to measure area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24hr) and maximum concentration observed in plasma (Cmax) of EE and NGMN. Comparability would be declared if the 90% confidence intervals for the geometric mean ratio of AUC0-24hr and Cmax in the absence and presence of laropiprant were within predefined bounds (0.80-1.25). The estimated geometric mean ratios (90% confidence intervals) of EE and NGMN, respectively, were 1.08 (1.04-1.13) and 0.97 (0.94-0.99) for AUC0-24hr and 1.16 (1.06-1.27) and 1.00 (0.94-1.06) for Cmax. The 90% confidence intervals for the geometric mean ratio of EE Cmax minimally exceeded the prespecified bounds; the other relevant pharmacokinetic parameters fell within the predefined bounds. Coadministration of 40 mg laropiprant with the oral contraceptive did not lead to clinically meaningful alterations in the pharmacokinetics of EE or NGMN.
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PMID:Effect of laropiprant, a PGD2 receptor 1 antagonist, on estradiol and norgestimate pharmacokinetics after oral contraceptive administration in women. 1994 Jun 9