The pharmacokinetics of cerivastatin in patients on chronic hemodialysis

Mück, Wolfgang; Park, S; Jäger, Wolfgang; Voith, Barbara; Wandel, E; Galle, PR; Schwarting, Andreas

doi:10.5414/cpp39192

Cited by 6 publications

(2 citation statements)

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“…The halflives of both parent drug and metabolites remain unaffected without accumulation under repeated dosage. In addition, cerivastatin clearance is not increased by concurrent dialysis as would be predicted from the high plasma protein-binding without significant difference in cerivastatin exposure between the dialysis and the dialysis-free profile days (Mü ck et al, 2001). 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).…”

Section: Statins and Cancer: Pros And Consmentioning

confidence: 90%

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Gazzerro

Proto²,

Gangemi³

et al. 2011

Pharmacol Rev

398

370

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Section: Statins and Cancer: Pros And Consmentioning

confidence: 90%

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Gazzerro

Proto²,

Gangemi³

et al. 2011

Pharmacol Rev

398

370

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“…The polymorphic cytochrome P450 2C8 is present at relatively high levels in most human livers [2][3][4][5] and has been demonstrated to be involved in the metabolism of several therapeutically important drugs, including amiodarone, 6 amodiaquine, 7 paclitaxel, 8 all-trans retinoic acid, 9 troglitazone, 10 rosiglitazone, 11,12 repaglinide, 2,13,14 verapamil, 15 and cerivastatin. 16 Recent in vivo studies have demonstrated the importance of CYP2C8-mediated metabolism as a target of drug-drug interactions. Reports of CYP2C8 inhibition by gemfi-…”

mentioning

confidence: 99%

Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8

Walsky

Gaman

Obach

2005

The Journal of Clinical Pharma

160

140

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Cytochrome P450 2C8 is involved in the metabolism of drugs such as paclitaxel, repaglinide, rosiglitazone, and cerivastatin, among others. An in vitro assessment of 209 frequently prescribed drugs and related xenobiotics was carried out to examine their potential to inhibit CYP2C8. A validated sensitive, moderate-throughput high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay was used to detect N-desethylamodiaquine, the CYP2C8-derived major metabolite of amodiaquine metabolism, using heterologously expressed recombinant CYP2C8 (rhCYP2C8) and pooled human liver microsomes. The 209 drugs were first tested at 30 muM for their ability to inhibit rhCYP2C8. Forty-eight compounds exhibited greater than 50% inhibition and were further evaluated for measurement of IC50. The six most potent inhibitors (IC50 <1 microM) from this set were measured for IC50 in pooled human liver microsomes, and the most potent inhibitor identified was the leukotriene receptor antagonist, montelukast (IC50 = 19.6 nM). Inhibitors of CYP2C8 were identified from a wide variety of therapeutic classes, with no single class predominating. Other potent inhibitors included candesartan cilexetil (cyclohexylcarbonate ester prodrug of candesartan), zafirlukast, clotrimazole, felodipine, and mometasone furoate. Seventeen moderate inhibitors of rhCYP2C8 (1 < IC50 < 10 microM) included salmeterol, raloxifene, fenofibrate, ritonavir, levothyroxine, tamoxifen, loratadine, quercetin, oxybutynin, medroxyprogesterone, simvastatin, ketoconazole, ethinyl estradiol, spironolactone, lovastatin, nifedipine, and irbesartan. These in vitro data were used along with clinical pharmacokinetic information in predicting potential drug-drug interactions that could occur by inhibition of CYP2C8. Although almost all drugs tested are not expected to cause drug interactions via inhibition of CYP2C8, montelukast was identified as being of concern as a potential inhibitor of clinical relevance. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which CYP2C8 is involved in metabolism and warrant investigation of the possibility of clinical drug interactions mediated by inhibition of this enzyme.

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