Therapeutic drug monitoring
-
Randomized Controlled Trial
Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring.
The objective of this study was to develop a population model of the pharmacokinetics (PK) of caffeine after orogastric or intravenous administration to extremely premature neonates with apnea of prematurity who were to undergo extubation from ventilation. Infants of gestational age <30 weeks were randomly allocated to receive maintenance caffeine citrate dosing of either 5 or 20 mg/kg/d. Four blood samples were drawn at prerandomized times from each infant during caffeine treatment. ⋯ This study established that the elimination of caffeine was severely depressed in extremely premature infants but increased nonlinearly after birth up to age 6 weeks. Caffeine was completely absorbed, which has favorable implications for switching between intravenous and orogastric routes. The interoccasion variability about CL was twice the interindividual variability, which, among other factors, indicates that routine serum concentration monitoring of caffeine in these patients is not warranted.
-
Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by > or =10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed. ⋯ Based on these data, the majority of critically ill patients would not be predicted to achieve the PD target under current dosing regimens. This may be a result of intensive care unit patients having a larger volume of distribution than reported in the literature. Future recommendations for treating gram-negative infections in the MICU population include using initial doses of 7 mg/kg of either gentamicin or tobramycin, measuring Cmax after the first dose, and determining MIC for the pathogen(s) with adjustment of subsequent doses to achieve the PD target.
-
In Europe, the misuse of gamma-hydroxybutyric acid (GHB) and its analogues has increased within the recent years. Here, 2 fatalities and 1 nonfatal intoxication resulting from ingestion of gamma-butyrolactone (GBL), a precursor of GHB, are presented. GHB was quantified involving the conversion to GBL by application of a gas chromatography-mass spectrometry (GC/MS) method. ⋯ The cause of death in each case was attributed to GHB intoxication; the manner of death was suicide in the first case and accidental in the second one. Another yet nonfatal GHB intoxication was reported by an emergency department concerning a 36-year-old woman who was hospitalized due to her comatose state and loss of adverse effects reflexes. Here nail polish remover pads were used as source for GBL.