Efficacy and plasma drug concentrations with nondaily dosing of rosuvastatin

Nondaily statin dosing is an alternative for patients unable to tolerate daily dosing. The higher potency and longer half-life of rosuvastatin lends itself to this regimen. The basis of this improved tolerability is not understood, but might be related to lower plasma drug concentrations. We examined the efficacy of nondaily rosuvastatin in previously statin-intolerant patients and determined plasma drug concentrations at various dose regimens.

A retrospective analysis at a specialty lipid clinic identified 58 patients eligible for evaluation after therapy with nondaily rosuvastatin. Plasma rosuvastatin levels were measured by liquid chromatography-mass spectrometry in 12 patients taking 10 mg nondaily rosuvastatin and in 11 and 12 age- and sex-matched patients taking 10 mg and 5 mg rosuvastatin daily, respectively. Whole body cholesterol synthesis was estimated from serum lathosterol measured by liquid chromatography-mass spectrometry.

In patients with a previous history of statin intolerance, nondaily rosuvastatin (average of 29.4 mg per week) lowered low-density lipoprotein cholesterol by 34.4 ± 21.3% (P < 0.001). Serum lathosterol levels were significantly higher in patients on nondaily regimens, as expected. However, mean plasma rosuvastatin levels of patients taking 10 mg nondaily did not significantly differ from those taking 10 mg daily.

In statin intolerant patients, nondaily rosuvastatin resulted in clinically relevant reductions in low-density lipoprotein cholesterol levels, with improved compliance. Whole body cholesterol synthesis was higher in patients taking nondaily rosuvastatin, but no differences in plasma drug concentrations were observed, suggesting that the improved tolerability was independent of plasma rosuvastatin levels.