Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Sep 2010
Randomized Controlled TrialGrapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren.
In a randomized crossover study, 11 healthy volunteers ingested 200 ml of grapefruit juice or water three times a day for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Grapefruit juice reduced aliskiren peak plasma concentration (C(max)) by 81% (range, 42-91%, P < 0.001), area under the plasma aliskiren concentration-time curve (AUC)(0-infinity) by 61% (range, 15-72%, P < 0.001), and elimination half-life (t(1/2)) from 26.1 to 23.6 h (P = 0.020). Therefore, concomitant use of aliskiren and grapefruit juice is best avoided.
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Clin. Pharmacol. Ther. · Sep 2010
The specialty of medical toxicology: beyond poisonous arrows and activated charcoal.
Medical toxicology is a subspecialty focusing on the diagnosis, management and prevention of poisoning effects due to medications, occupational and environmental toxins and xenobiotics, radiological and biological agents. This subspecialty provides an array of opportunities for physicians to care for patients in different settings: medication overdoses, substance abuse management, adverse drug events, exposures to industrial chemical products, and envenomations. Many medical toxicologists work in the pharmaceutical industry and in many government agencies such as as the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency (EPA), the US Food and Drug Administration (FDA), and the Department of Homeland Security.
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Levamisole has increasingly been discovered in street cocaine as an adulterant. Recent reports have linked levamisole in street cocaine to agranulocytosis in cocaine users. It is well known that agranulocytosis is associated with therapeutic use of levamisole, and this may have led to the withdrawal of the drug from the US market. ⋯ This may be supported by the recent report of metabolism of levamisole to aminorex in racehorses. Aminorex and related compounds, specifically 4-methylaminorex, or "ice," have high abuse potential because of their amphetamine-like pharmacological activity. This metabolism has not been reported in humans, and therefore the intended role of levamisole in street cocaine remains an enigma.