Entrapment efficiency and initial release of phenylbutazone from nanocapsules prepared from different polyesters.

Several formulations of poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactic-co-glycolic acid) (PLGA) nanocapsules containing phenylbutazone were prepared according to the interfacial deposition technique. These formulations differed in the type of polymer used to form the shell of the nanocapsules. Analysis of particle size distribution and encapsulation efficiency of the nanocapsules revealed that the type and molecular weight of polyester used were the main factors influencing these properties. PLA had the highest encapsulation efficiency with the best reproducibility. From in vitro release studies, a small amount of drug release was observed at pH 7.4. However, in the gastric medium, an important burst effect occurred and was highest with the PLGAs and lowest with PCL, suggesting that drug release from these systems is affected by the type of polymer and the environmental conditions. The two formulations of phenylbutazone-loaded nanocapsules should be evaluated based on PCL and PLA in vivo in order to determine to what extent they are able to reduce the local side effects of this drug.

Determination of sinefungin in rat plasma by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method for the determination of sinefungin, a new antiprotozoal drug, in rat plasma has been developed and validated. Sample preparation was performed at 4 degrees C by deproteinization with acetonitrile. Vidarabine was used as an internal standard. Both sinefungin and vidarabine were separated on a C18 column with a mobile phase of ammonium dihydrogenphosphate-acetonitrile (95:5, v/v) and detected by ultraviolet absorbance at 260 nm. Recoveries of sinefungin from plasma were 75 +/- 3.2% and 81 +/- 4.8% following dosage at concentrations of 10 micrograms/ml and 30 micrograms/ml, respectively. Using 250 microliters of rat plasma, the limit of quantitation was 1 microgram/ml sinefungin, and the assay was linear from 1 to 30 micrograms/ml. This method appears sensitive enough to be used in further pharmacokinetic studies of sinefungin in animal models.

Pharmacokinetic studies of ambenonium chloride in patients with myasthenia gravis.

Serum levels of ambenonium chloride (AC) were monitored in 4 myasthenic patients. This determination revealed important intraindividual variations (up to 10-fold) over a period of 24 h. Levels varied considerably between different patients (maximum serum concentration of ambenonium chloride ranged from 0.129 to 0.812 micrograms/ml) and no correlation between the daily dose and the AUC was found. These characteristic properties of ambenonium chloride could explain the erratic pattern of bioavailability observed as well as the difficulty in controlling the disease in some patients.

Pharmacokinetics of ambenonium chloride in dogs after intravenous and oral administration.

Plasma concentrations of ambenonium chloride (Mytélase) were studied, using a high pressure liquid chromatographic technique, in 11 dogs, after intravenous or oral administration of the drug. The results found suggest a complex multi-compartment storage with several periodical releases in general circulation.