Pilot study in humans on the pharmacokinetics and safety of propofol 6% SAZN.

In a pilot study on the first application of Propofol 6% SAZN in humans, the pharmacokinetics and safety of the new product seem to be similar to those of Propofol 1% SAZN and Diprivan-10 after bolus injection. The results will have to be confirmed in a larger clinical study in order to develop Propofol 6% SAZN as an alternative for Diprivan-10.

Methemoglobinemia as an uncommon cause of cyanosis.

Cyanosis is usually caused by decreased arterial oxygen saturation due to pulmonary or cardiac diseases. Methemoglobinemia is a rare cause, sometimes with lethal outcome. Two patients are described, both with an unremarkable cardiopulmonary history, presented with severe cyanosis due to aniline-induced methemoglobinemia that developed at work. The symptoms and the treatment of methemoglobinemia are discussed.

Influence of different fat emulsion-based intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol.

PURPOSE: The influence of different intravenous formulations on the pharmacokinetics and pharmacodynamics of propofol was investigated using the effect on the EEG (11.5-30 Hz) as pharmacodynamic endpoint. METHODS: Propofol was administered as an intravenous bolus infusion (30 mg/kg in 5 min) or as a continuous infusion (150 mg/kg in 5 hours) in chronically instrumented male rats. Propofol was formulated as a 1% emulsion in an Intralipid 10%-like fat emulsion (Diprivan-10, D) or as a 1%- or 6% emulsion in Lipofundin MCT/LCT-10% (P1% and P6%, respectively). EEG was recorded continuously and arterial blood samples were collected serially for the determination of propofol concentrations using HPLC. RESULTS: Following bolus infusion, the pharmacokinetics of the various propofol emulsions could adequately be described by a two-compartmental pharmacokinetic model. The average values for clearance (Cl), volume of distribution at steady-state (Vd,ss) and terminal half-life (t1/2, lambda 2) were 107 +/- 4 ml/min/kg, 1.38 +/- 0.06 l/kg and 16 +/- 1 min, respectively (mean +/- S.E. n = 22). No significant differences were observed between the three propofol formulations. After continuous infusion these values were 112 +/- 11 ml/min/kg, 5.19 +/- 0.41 l/kg and 45 +/- 3 min, respectively (mean +/- S.E., n = 20) with again no statistically significant differences between the three propofol formulations. Comparison between the bolus- and the continuous infusion revealed a statistically significant difference for both Vd,ss and t1/2, lambda 2 (p < 0.05), whereas Cl remained unchanged. In all treatment groups infusion of propofol resulted in a burst-suppression type of EEG. A profound hysteresis loop was observed between blood concentrations and EEG effect for all formulations. The hysteresis was minimized by a semi-parametric method and resulted in a biphasic concentration-effect relationship of propofol that was described non-parametrically. For P6% a larger rate constant onset of drug effect (t1/2,keo) was observed compared to the other propofol formulations (p < 0.05). CONCLUSIONS: The pharmacokinetics and pharmacodynamics of propofol are not affected by to a large extent the type of emulsion nor by the concentration of propofol in the intravenous formulation.

Determination of propofol in low-volume samples by high-performance liquid chromatography with fluorescence detection.

In order to determine propofol in rat whole-blood samples of 50 microl, we developed a rapid, simple and reliable method which is characterized by precipitation of blood elements with acetonitrile and submission of the supernatant to HPLC analysis with fluorescence detection. The method described is linear from 0.4 to 40 mg/l and the relative standard deviations in this concentration range are less than 10%. The limit of quantification proved to be 0.4 mg/l. Blood constituents do not interfere with the assay.