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The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).

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Recent work in the area of model-order reduction for RLC interconnect networks has been focused on building reduced-order models that preserve the circuittheoretic properties of the network, such as stability, passivity, and synthesizability {1, 2, 3, 4, 5}. Passivity is the one circuit-theoretic property that is vital for the successful simulation of a large circuit netlist containing reduced-order models of its interconnect networks. Non-passive reduced-order models may lead to instabilities even if they are themselves stable. In this paper, we address the problem of guaranteeing the accuracy and passivity of reduced-order models of multipart RLC networks at any finite number of e:cpansion points. The novel passivity-preserving modelorder reduction scheme is a block version of the rational Arnoldi algorithm [6, 7}. The scheme reduces to that of {5] when applied to a single e:cpansion point at zero frequency. Although the treatment of this paper is restricted to expansion points that are on the negative real a:cis, it is shown that the resulting passive reduced-order model is superior in accuracy to the one that would result from e:cpanding the original model around a single point. Nyquist plots are used to illustrate both the passivity and the accuracy of the reducedorder models.

Fenofibrate is a third-generation fibric acid derivative indicated as a monotherapy to reduce elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, and apolipoprotein B; to increase high-density lipoprotein cholesterol in patients with primary hyperlipidemia or mixed dyslipidemia; and to reduce triglycerides in patients with severe hypertriglyceridemia. In this review, the key characteristics of available fenofibrate formulations are examined. A literature search was conducted, focusing on comparative studies examining bioavailability, food effects, absorption, and lipid efficacy. Fenofibrate is highly lipophilic, virtually insoluble in water, and poorly absorbed. Coadministration with meals was necessary to maximize bioavailability of early formulations. Micronized and nanoparticle formulations of fenofibrate with reduced particle sizes were developed, resulting in greater solubility, improved bioavailability, and in some cases, the ability to be given irrespective of food. A recently introduced hydrophilic choline salt of fenofibric acid also can be taken without regard to meals, is absorbed throughout the gastrointestinal tract, has the highest bioavailability among marketed formulations, and is approved for coadministration with a statin. Differences in bioavailability of fenofibrate formulations have resulted in low-dose (40 -67) mg and standard-dose (120 -200 mg) formulations. Different formulations are not equivalent on a milligram-to-milligram basis. In order to prevent medication errors, resulting in underdosing or overdosing with attendant consequences, it is important for healthcare providers to recognize that the formulations of fenofibrate and fenofibric acid that are currently available vary substantially in relation to food effect, equivalency on a milligram-to-milligram basis, and indication to be coadministered with a statin.