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Abstract Title:

In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors.

Abstract Source:

Pharm Res. 1994 Feb ;11(2):305-11. PMID: 8165193

Abstract Author(s):

A Saheki, T Terasaki, I Tamai, A Tsuji

Article Affiliation:

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.

Abstract:

Among the HMG-CoA reductase inhibitors, lovastatin and simvastatin have central nervous system (CNS) side effects, such as sleep disturbance, whereas pravastatin does not. This difference in CNS side effects may be due to a difference in blood-brain barrier (BBB) permeability among these inhibitors. To test this hypothesis, we compared the BBB transport ability of HMG-CoA reductase inhibitors by using an in vivo brain perfusion technique in rats and an in vitro culture system of bovine brain capillary endothelial cells. The in vivo BBB permeability coefficients of the lipophilic inhibitors, [14C]lovastatin and [14C]simvastatin, were high. In contrast, that of the hydrophilic inhibitor, [14C]pravastatin, was low and not significantly different from that of [14C]sucrose, an extracellular space marker. Similarly, the in vitro BBB permeability coefficients of [14C]lovastatin and [1C]simvastatin were high, while that of [14C]-pravastatin was low. The in vivo and in vitro transcellular permeabilities obtained for HMG-CoA reductase inhibitors were comparable. This study shows that the BBB permeability correlates with the CNS side effects of the HMG-CoA reductase inhibitors.

Study Type : Animal Study

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Sayer Ji
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