Because the plasma exposure levels of rosuvastatin in Asians are generally twice those in Caucasians, the starting dose for Asians in the United States is set to half of that for non-Asians. However, the precise role of ethnicity in the clearance of rosuvastatin has not yet been clarified. This review focuses on ethnic variability in the clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (statins) and angiotensin II receptor antagonists. The mechanisms of such variability are discussed quantitatively, with building a hypothetical model for pravastatin, and validated against other statins. Our analyses suggest that the ethnic variability in the plasma exposure of statins cannot be explained only by the difference in the allele frequencies of organic anion-transporting polypeptide (OATP)1B1 and breast cancer resistance protein (BCRP), and the intrinsic ethnic variability in the activity of OATP1B1 (the ratio of Japanese/Caucasians is 0.584) must be considered. Further work and validation with additional data will clarify the applicability of this model to other OATP1B1 substrates.

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Ruminal bacteria and protozoa, and cell-free rumen fluid, were tested for the presence of enzymes involved in the degradation of the fungal cell wall. Protozoal homogenate obtained by ultrasonication showed chitinase (EC 3.2.1.14) and N-acetyl-/&glucosaminidase (EC 3.2.1.52) activities when assayed with f luorogenic 4-methylumbel liferyl substrates. The chitinase activity was predominantly of the 'exo'-type. Lysozyme (EC 3.2.1 .17) and 1,3-~glucanase (EC 3.2.1.39) activities were also present in this fraction. A l l these activities, except lysozyme activity, were recovered mainly in the supernatant fraction of the homogenate (approximately 85 O/ O of the total activity). Lysozyme showed the same amount of activity in the precipitate and s u per n a t a n t f r a ct i on s . B a c t e r i a I h o m og e n a t e s had N-ace t y I -p-g I u cosa m i n i d a se activity in both supernatant and precipitate fractions. The specific activity was one-third that of the protozoa. Bacteria able to grow in a medium with c h i t i n as the sole carbon source were recognized and counted. Cell-free rumen fluid was unable to degrade any of the substrates tested.