Therapeutic drug monitoring
-
Smoking in pregnancy is associated with serious perinatal risks, leading to attempts to prevent smoking with the use of nicotine-replacement therapy (NRT). After more than a decade of studies failing to show the effectiveness of NRT for smoking cessation in pregnancy, a recent large, randomized trial has clearly shown that the failure may be caused by >90% dropout rate. ⋯ But to be effective in smoking cessation, any drug has to be taken by the patients. Can we overcome the dismal rates of pregnant women's adherence to NRT, so we can save unborn babies from the serious risks associated with their mothers' smoking?
-
Multicenter Study
Minimization of the preanalytical error in pharmacokinetic analyses and therapeutic drug monitoring: focus on IV drug administration.
The conduct of multicenter pharmacokinetic (PK) analyses for long-established drugs entails specific problems, because samples have to be obtained within daily clinical practice. Practices for intravenous (IV) drug administration vary between hospitals, including the use of different infusion devices, the use of infusion line systems with different line volumes, and different priming and rinsing procedures. ⋯ The choice of the infusion apparatus, standardized infusion systems, and standardized operating procedures for drug administration are important when performing postmarketing PK analyses in multicentric studies.
-
Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years.
In children, a large variability in pharmacokinetics of midazolam, a cytochrome P450 3A4/5 (CYP3A4/5) enzyme substrate, has been described, which cannot be explained by age-related changes alone. In this study, these age-related changes are studied in relation to other covariates to explain the variability in the pharmacokinetics of midazolam in children. ⋯ From infancy to adolescence, critical illness seems to be a major determinant of midazolam clearance, which may result from reduced CYP3A4/5 activity due to inflammation. This may have important implications for dosing of midazolam and other CYP3A drug substrates in critically ill children.
-
Clinical Trial
A simplified oral flucloxacillin absorption test for patients requiring long-term treatment.
Patients with severe methicillin-sensitive Staphylococcus aureus infections are effectively treated with initial continuous intravenous (iv) flucloxacillin followed by oral maintenance therapy. As the absorption of oral flucloxacillin is variable, an oral absorption test (OAT) is used to ensure efficacious therapy. The classical OAT (test A) requires overnight fasting, interruption of iv therapy, and is laborious. We designed a simplified OAT (test B) in which iv therapy is continued and oral dosing is performed after a 1-hour fast. ⋯ We designed a simplified OAT that performs well and can be implemented easily. This test may be helpful to rationally and effectively treat patients with severe methicillin-sensitive S. aureus infections with an orally administered small-spectrum antibiotic.