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The result is that the background, even though it may be a bit blurry due to a slowAbstract The human circadian system is not a single “on” and “off” clock. Rather, there is an exquisitely sophisticated regulation of the timing of daily biochemical reactions, metabolic processes, and behavioral activities. The discovery that shifts in circadian timing have a significant impact on human health and well being has created a paradigm shift in sleep medicine. The clock is complex, and the mechanisms that regulate the timing of the circadian cycle are still being determined. This chapter will discuss how the clockworks are regulated, what sleep medications target in the brain and the role of the clock in sleep and sleep-related disorders.The relationship between absorption, metabolism, and tissue distribution of a poorly water soluble drug: troglitazone, a hypoglycemic agent, in rats. The concentration of troglitazone and its major metabolite, M-2, were measured in the plasma, liver, bile, intestine, and urine at various time intervals following administration of a single oral dose of troglitazone (50 mg/kg) to male Sprague-Dawley rats. The absolute bioavailability of troglitazone was approximately 54%. The distribution of troglitazone in the body follows a biphasic pattern. Troglitazone was rapidly and extensively absorbed from the intestine. Troglitazone and M-2 were rapidly metabolized to glucuronides in the liver. The plasma clearance and tissue distribution of troglitazone and M-2 were much slower than that of the parent compound. A correlation was observed between the lipophilicity of the drug and the relative distribution of the drug in various tissues. The bioavailability of M-2 was much lower than that of the parent compound. M-2 was rapidly excreted in the bile and feces following oral administration. The data reported indicate that the therapeutic utility of the troglitazone should be limited by the absolute bioavailability of the compound.Valentine's Day video, 2020 The article is available only to paid subscribers The article is closed to new "Valentine's Day video, 2020" subscribers. Thank you for subscribing. Valentine's Day video, 2020 February 14, 2020 On this day in history, in 1762, an event took place in England that would cause worldwide excitement.