Determination of plasma concentration reference ranges for oral aripiprazole, olanzapine, and quetiapine

Schizophrenia is a common disease which is commonly managed using antipsychotic medications (APS). Inadequate response and lack of adherence often prevent optimal therapeutic effectiveness. Monitoring APS concentrations can be useful to help improve outcomes for the patient. The aim of this study was to develop "reference ranges" for oral aripiprazole, olanzapine, and quetiapine to allow clinicians to understand expected variability in patients treated with APS. The reference ranges were constructed to account for different oral doses, sampling times, and variability both between, and within, subjects. Population pharmacokinetic models were used to simulate plasma concentrations over time under different doses and population demographics. The references were validated against external data both numerically and graphically. Reference ranges for oral aripiprazole, olanzapine, and quetiapine were derived and successfully validated against the external data. The 80% reference range for aripiprazole following a 2-mg oral dose was 14.7-41.6 ng/mL 0-4 h post dose and 10.6-37.1 ng/mL 20-24 h post dose. These ranges increased to 221-624 ng/mL 0-4 h post dose following administration of a 30-mg dose, and 159-557 ng/mL 20-24 h post dose. The 80% reference range 0-4 h post dose was 22.5-67.1 ng/mL following a 15-mg dose once daily of oral olanzapine, and 179-768 ng/mL following a 150-mg dose once daily of oral quetiapine. Comparing individual patients' APS levels with reference ranges, along with a full clinical assessment, could provide important insights to help a clinician optimize APS therapy

Overcoming phase 1 delays: the critical component of obstetric fistula prevention programs in resource-poor countries

<p>Abstract</p> <p>Background</p> <p>An obstetric fistula is a traumatic childbirth injury that occurs when labor is obstructed and delivery is delayed. Prolonged obstructed labor leads to the destruction of the tissues that normally separate the bladder from the vagina and creates a passageway (fistula) through which urine leaks continuously. Women with a fistula become social outcasts. Universal high-quality maternity care has eliminated the obstetric fistula in wealthy countries, but millions of women in resource-poor nations still experience prolonged labor and tens of thousands of new fistula sufferers are added to the millions of pre-existing cases each year. This article discusses fistula prevention in developing countries, focusing on the factors which delay treatment of prolonged labor.</p> <p>Discussion</p> <p>Obstetric fistulas can be prevented through contraception, avoiding obstructed labor, or improving outcomes for women who develop obstructed labor. Contraception is of little use to women who are already pregnant and there is no reliable screening test to predict obstruction in advance of labor. Improving the outcome of obstructed labor depends on prompt diagnosis and timely intervention (usually by cesarean section). Because obstetric fistulas are caused by tissue compression, the time interval from obstruction to delivery is critical. This time interval is often extended by delays in deciding to seek care, delays in arriving at a hospital, and delays in accessing treatment after arrival. Communities can reasonably demand that governments and healthcare institutions improve the second (transportation) and third (treatment) phases of delay. Initial delays in seeking hospital care are caused by failure to recognize that labor is prolonged, confusion concerning what should be done (often the result of competing therapeutic pathways), lack of women’s agency, unfamiliarity with and fear of hospitals and the treatments they offer (especially surgery), and economic constraints on access to care.</p> <p>Summary</p> <p>Women in resource-poor countries will use institutional obstetric care when the services provided are valued more than the competing choices offered by a pluralistic medical system. The key to obstetric fistula prevention is competent obstetrical care delivered respectfully, promptly, and at affordable cost. The utilization of these services is driven largely by trust.</p