Atypical antipsychotic metabolism and excretion.

BACKGROUND: The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored. OBJECTIVE: To analyze the excretion profile of atypical antipsychotic agents and compare the overall magnitude of metabolism (changed vs. unchanged drug) and route of excretion (feces vs. urine). Secondary objectives include providing: 1) dosing information in hepatic and renal impairment, and 2) context of the specific enzymes and pathways involved in each agents' biotransformation. METHODS: Published literature and each manufacturer's radiolabeled drug absorption, distribution, metabolism and excretion data and U.S. prescribing information were reviewed. RESULTS: With the exception of paliperidone, atypical antipsychotics undergo extensive metabolism (i.e.,

Prevalence of the factor V leiden mutation in children and neonates with thromboembolic disease.

OBJECTIVE: Resistance to activated protein C (APC) has been identified as a risk factor for thrombotic disease in adults. In over 90% of cases, the basis for the APC resistance is a mutation in the coagulation factor V gene (factor V Leiden) that renders the protein more resistant to inactivation by APC. We sought to determine the prevalence of the factor V Leiden (FVL) mutation in neonates and children who had experienced an arterial or venous thromboembolic event. STUDY DESIGN: We retrospectively analyzed the clinical records of 33 neonates and 52 children with thromboembolic disease. Screening for the FVL mutation was performed by DNA analysis, allowing for identification of patients as normal, heterozygous, or homozygous. RESULTS: Of the 85 patients studied, 12 (14.1%) were heterozygous for FVL; none were homozygous. Of the 47 patients who had arterial central nervous system events, 8 (17%) were positive for the FVL mutation, including 6 of 22 (27%) neonates. Of those patients who had a venous thrombosis, 4 of 32 (12.5%) were FVL positive. None of the 85 patients had protein C deficiency, 3.5% had protein S deficiency, 1.2% had antithrombin III deficiency, and 16.5% had anti-phospholipid antibodies. CONCLUSION: These data suggest that the FVL mutation plays a role in the development of arterial and venous thrombotic events in neonates and children.

Migraine. Identifying and removing barriers to care.

The high levels of pain and disability associated with undiagnosed migraine or inadequate treatment of migraine offer a potential target for healthcare intervention. Both the individual patient and society are affected by decisions regarding which migraine sufferers are most in need of medical care. Pain is the most important symptom for the individual patient, but disability may be the most important consequence of migraine for an increasingly cost-conscious society. These two perspectives are the components of a migraine severity or impact measure being developed to define migraine sufferers most in need of care. The criteria for developing screening programs provide a context for evaluating healthcare interventions for migraine. Barriers to effective care occur on at least three levels: many people with migraine do not consult doctors; consulters may not receive the correct diagnosis; and even when the correct diagnosis is made, many migraineurs do not receive effective treatment. Screening and impact measures may help both to improve diagnosis and to determine which migraineurs are most in need of care. Public and physician education, screening, and impact measures might circumvent many of the barriers to effective care for people with migraine.