Pharmacokinetics of rosuvastatin in patients with end-stage kidney disease undergoing peritoneal dialysis.
TL;DR: It is concluded that pharmacokinetic profiles of rosuvastatin in patients undergoing CAPD are similar to those observed in healthy volunteers, but different from patients with Stages 4 - 5 chronic kidney disease.
Abstract: Patients undergoing dialysis treatment have a high incidence of dyslipidemia. Rosuvastatin is a potent statin drug that improves overall lipid profiles in dyslipidemic patients. However, the pharmacokinetics of rosuvastatin has not been studied in patients with end-stage kidney disease undergoing chronic peritoneal dialysis (PD). The goals of this study are to determine the pharmacokinetics and tolerability of a single oral dose of rosuvastatin in patients undergoing continuous ambulatory PD (CAPD). This was a nonrandomized, open-label, 1-week trial. Ten stable PD patients were given a single oral dose of rosuvastatin (10 mg). Serial blood samples were obtained over the next 48 hours, and the patients were followed for 1 week while they underwent CAPD. Rosuvastatin plasma concentration peaked (Cmax) at 3.68 +/- 2.3 ng/ml (geometric mean), 4.5 hours (median; range 2 - 6 hours) after oral dosing. The plasma concentration of rosuvastatin was 0.44 +/- 0.23 ng/ml at 24 hours (C24) and 0.14 +/- 0.07 ng/ml, with levels below the detectable range in 5 of 10 subjects, at 48 hours (C48). The area under the plasma concentration-time from 0 to 48 hours (AUC0-48) was 32.6 +/- 1.6 ng/ml/h. These pharmacokinetic profiles of rosuvastatin in CAPD patients are very similar to those observed in healthy volunteers, but different from patients with Stages 4 - 5 chronic kidney disease. A single oral dose of rosuvastatin was well tolerated in this small number of patients. We conclude that pharmacokinetic profiles of rosuvastatin in patients undergoing CAPD are similar to those observed in healthy volunteers. These findings suggest that a lower dose of rosuvastatin (<<= 10 mg) may be administered in CAPD patients without dose adjustment.
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TL;DR: The pharmacology of the statins is reviewed, providing a comprehensive update of the current knowledge of their effects on tissues, biological processes, and pathological conditions, and the disappointing evidence on the possible future use of statin-based drugs in cancer therapy is dissected.
Abstract: Statins, among the most commonly prescribed drugs worldwide, are cholesterol-lowering agents used to manage and prevent cardiovascular and coronary heart diseases. Recently, a multifaceted action in different physiological and pathological conditions has been also proposed for statins, beyond anti-inflammation and neuroprotection. Statins have been shown to act through cholesterol-dependent and -independent mechanisms and are able to affect several tissue functions and modulate specific signal transduction pathways that could account for statin pleiotropic effects. Typically, statins are prescribed in middle-aged or elderly patients in a therapeutic regimen covering a long life span during which metabolic processes, aging, and concomitant novel diseases, including cancer, could occur. In this context, safety, toxicity, interaction with other drugs, and the state of health have to be taken into account in subjects treated with statins. Some evidence has shown a dichotomous effect of statins with either cancer-inhibiting or -promoting effects. To date, clinical trials failed to demonstrate a reduced cancer occurrence in statin users and no sufficient data are available to define the long-term effects of statin use over a period of 10 years. Moreover, results from clinical trials performed to evaluate the therapeutic efficacy of statins in cancer did not suggest statin use as chemotherapeutic or adjuvant agents. Here, we reviewed the pharmacology of the statins, providing a comprehensive update of the current knowledge of their effects on tissues, biological processes, and pathological conditions, and we dissected the disappointing evidence on the possible future use of statin-based drugs in cancer therapy.
402 citations
Cites background from "Pharmacokinetics of rosuvastatin in..."
...Moreover, in patients with end-stage kidney disease undergoing continuous ambulatory peritoneal dialysis, the pharmacokinetic profile of rosuvastatin is very similar to that observed in healthy volunteers; therefore, a lower dose of rosuvastatin may be administered (Bologa et al., 2009)....
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TL;DR: Clinical pharmacokinetic studies are required to determine the optimal dosage of drugs in CKD and hemodialysis patients in order to decrease the incidence of adverse medication events in these patient populations.
Abstract: Introduction: Chronic kidney disease (CKD) is the progressive decline in renal function over time. Patients with end-stage renal disease require renal replacement therapy such as hemodialysis to support life. Hemodialysis patients require several medications to treat a variety of comorbid conditions. Polypharmacy accompanied by alterations in the pharmacokinetics of medications places hemodialysis patients at increased risk of drug accumulation and adverse events.Areas covered: We review alterations in the pharmacokinetics of drugs in hemodialysis patients. The major areas of pharmacokinetics, absorption, distribution, metabolism and excretion, are covered and, where appropriate, differences between dialysis patients and non-dialysis CKD patients are compared. In addition, we review the importance of drug dialyzability and its potential impact on drug efficacy. Finally, we describe important clinical examples demonstrating nonrenal drug clearance is significantly altered in CKD.Expert opinion: Decreases i...
66 citations
Cites result from "Pharmacokinetics of rosuvastatin in..."
...In contrast, studies in hemodialysis and peritoneal dialysis patients demonstrate no clinically relevant changes in rosuvastatin pharmacokinetics compared to patients with normal kidney function [98,99]....
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TL;DR: Rosuvastatin and pitavastatin have favorable pharmacokinetic and safety profiles as their disposition does not depend on or is only marginally influenced by cytochrome P450 (CYP) enzymes, thus potentially reducing the risk of drug–drug interactions of these two statins with other drugs known to inhibit CYP enzymes.
Abstract: Introduction: Statins are the cornerstone of lipid-lowering therapy to reduce the risk of coronary heart disease. Rosuvastatin and pitavastatin are the two recently developed statins with less potential for drug interaction resulting in improved safety profiles. Areas covered: This review summarizes the pharmacokinetics and drug interactions of rosuvastatin and pitavastatin. The materials reviewed were identified by searching PubMed for publications using ‘rosuvastatin', ‘pitavastatin', ‘statins', ‘pharmacokinetics' and ‘drug interaction' as the search terms. Expert opinion: Rosuvastatin and pitavastatin have favorable pharmacokinetic and safety profiles as their disposition does not depend on or is only marginally influenced by cytochrome P450 (CYP) enzymes, thus potentially reducing the risk of drug–drug interactions of these two statins with other drugs known to inhibit CYP enzymes. However, drug transporters play a significant role in the disposition of rosuvastatin and pitavastatin and drug interacti...
31 citations
Cites background from "Pharmacokinetics of rosuvastatin in..."
...In patients with end-stage kidney disease on continuous ambulatory peritoneal dialysis, the systemic exposure following a single oral dose of rosuvastatin 10 mg was similar to that observed in healthy volunteers [28]....
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TL;DR: Although the results of trials are conflicting, it is suggested that the benefits of statin use outweigh the drawbacks in patients with early-stage CKD, when the benefits can be effectively predicted.
Abstract: Importance of the field: Patients with end-stage renal disease are at high risk of developing cardiovascular disease, which is characterized by early onset and rapid progression of atherosclerosis. Some analyses of large clinical trials have revealed that statins might reduce all-cause mortality and cardiovascular (CV) events in patients with chronic kidney disease (CKD). Preliminary studies have also suggested that they can reduce contrast-induced nephropathy (CIN) and the rate of loss of kidney function. However, the results concerning the efficacy and safety of statin therapy in patients with CKD, especially in those on renal replacement therapy, are still controversial.Areas covered in this review: This review contains data on the atherosclerotic risk in patients with CKD; the role of statins in the reduction of CV risk in patients with CKD; the role of CIN; the effects of statins on retarding the progression of CKD; and the efficacy of statin therapy in CKD, dialysis and renal-transplant patients. We...
30 citations
Cites background or result from "Pharmacokinetics of rosuvastatin in..."
...Moreover, it has been shown that the elimination time of rosuvastatin is longer in patients with stage IV CKD or in those receiving HD than in normal volunteers, and the steady-state plasma concentrations in patients receiving long-term HD were approximately 50% higher than in healthy volunteers [2,87]....
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...[2] demonstrated that the pharmacokinetic profiles of rosuvastatin in a single oral dose (10 mg) in patients undergoing peritoneal dialysis were similar to those found in healthy volunteers after oral administration of this drug....
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...The discrepancies between the results obtained from patients with advanced CKD and patients receiving peritoneal dialysis may be due to the fact that rosuvastatin might be partially cleared by the dialysis [2]....
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...This complication is the leading cause of patient mortality [1,2]....
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TL;DR: Given the more 'metabolic syndrome like' profile of lipids in stage 5 CKD adjunctive methods such as fibrates and omega-3 is discussed, however no good data is available in this group on outcomes with these agents.
Abstract: Treatment of cholesterol in people with advanced stage chronic kidney disease (CKD) clearly reduces cardiovascular risk; however, it does not significantly slow nephropathy progression. Moreover, cholesterol reduction does not reduce mortality in people on dialysis. In general, cholesterol reduction is very important for reducing cardiovascular risk in people with GFR values >15 ml/min who are not on dialysis. There are many reasons for the lack cardiovascular risk reduction with cholesterol lowering in dialysis patients including a defective HDL and higher than usual oxidation rates of LDL. The reviews some of the biochemistry of lipids in uremia and discusses the randomized trial data that support these statements and provides greater detail regarding use of statin in patients with stages 4 and 5 CKD. Caution should be used in dosing statins in stage 3b or higher CKD. Specifically, all statins except for atorvastatin and pravastatin need dose reductions due to safety issues. Given the more 'metabolic syndrome like' profile of lipids in stage 5 CKD adjunctive methods such as fibrates and omega-3 is discussed, however no good data are available in this group on outcomes with these agents.
24 citations