Solubilization and wetting effects of bile salts on the dissolution of steroids.

The ability of sodium taurocholate to increase the initial dissolution rate of five steroids was studied in terms of effects on solubility, wetting, and diffusion coefficient. For all compounds, wetting effects predominated over solubilization effects at bile salt concentrations representative of the fasted state. For hydrocortisone, triamcinolone, betamethasone, and dexamethasone, this trend also continued at the higher bile salt concentrations typical of the fed state. Bile salts solubilized these compounds by a factor of two or less, and diffusivity changes were negligible at bile salt concentrations up to 30 mM. For the more lipophilic danazol, the wetting effects were small and of importance only at premicellar levels of bile salt. At higher concentrations, the increase in solubility was the predominant factor. Incorporation into micelles appeared to decrease the diffusivity slightly, but this was important only at bile salts concentrations of 15 mM or higher. In conclusion, it appears that even within a series of structurally related compounds the mechanism by which bile salts mediate increases in dissolution rate can differ considerably.

Particulate contamination in plastic ampoules.

Plastic ampoules of Water for Injections, JP, and Injection Sodium Chloride, JP, were investigated to determine their particle load. Four batches were studied. The ampoules were twist-opened as they would be in the clinical setting and the total particle load, both inherent and that created in opening, was determined by reading the contents with a HIAC 420 particle counter with a CMB 60 sensor. The total particle content was found to be minimal, easily complying with world L.V.P. standards and the S.V.P. standard of the USP XXI. The number of particles found in these opened plastic ampoules was significantly lower than that found in clinically snap-opened glass ampoules and also slightly lower than that found in laboratory heat-opened glass ampoules. Whilst the plastic ampoule has a restricted application because it is not suitable for all drugs, it is concluded that when they are used as the immediate container for Water for Injections and Injection Sodium Chloride they are highly effective in reducing the particulate contamination generated in opening.

Plasma bupivacaine concentrations following lumbar epidural anaesthesia in children.

Plasma levels of bupivacaine were measured following lumbar epidural administration of 3 mg/kg of 0.5% plain solution in sixteen children. The peak levels were generally between 1.0 and 2 micrograms/ml, the highest being 2.9 micrograms/ml. No manifestations of toxicity were observed. There was a significant positive correlation between peak plasma levels and increasing age.

The influence of age on lignocaine pharmacokinetics in young puppies.

Eight mongrel puppies were studied at intervals of a few weeks. Lignocaine 4 mg/kg was infused over 60 seconds. Frequent samples were taken over 30 minutes for plasma lignocaine assay. Initially the concentrations were significantly higher in the oldest group (178-191 days) but after 10 minutes the youngest group (3-16 days) had significantly higher levels than the other groups. Pharmacokinetic data derived included the rate constants k21, k12 (drug movement between two compartments), k10 (elimination from the central compartment), and the volume of distribution (V beta). The elimination rate constant k10 was significantly lower in Group 1 (3-16 days) than all other groups and Group 2 (37-57 days) was lower than Group 4 (178-191 days). The calculated beta half-life was significantly longer in the youngest group than the others. There was no significant difference in the volume of distribution between these age groups--up to 6 months.

Particulate contamination of Australian ampoules.

Theoretical predictions and computer simulations indicate that it may be impossible to achieve values of the coefficient of variation usually found in large volume parenterals (LVP) when the intrinsic particulate contamination in small volume parenterals (SVP) is investigated. Snap-opened ampoules from Australian manufacturers containing 5, 10 or 20 ml Water for Injections or Sodium Chloride Injection had a high level of particulate contamination, although within the USP XXI SVP limits. Heat-opened ampoules had much lower levels of contamination which were generally below the official LVP limits. Counts ml-1 were typically less than 10 and less than 1 for 5 and 20 micron particles, respectively. Coefficients of variation of the 5 micron data from an ampoule in any batch examined, typically ranged over 30-70%. Statistical analysis of the 5 micron data indicates significant differences between batches. Occasional ampoules had higher 5 micron counts than others in the same batch. At no time were the particulate contamination levels considered to be clinically important.

The influence of age on plasma lignocaine levels following tracheal spray in young dogs.

A study was conducted in puppies of one litter beginning before they were three weeks old and repeated up to six times in the first four months of life to determine whether any age-related changes in peak plasma lignocaine levels occurred following tracheal spray. These were significantly higher in the youngest group (less than 20 days) than in dogs 2-3 months of age. There was a significant negative correlation between peak plasma levels and age up to four months. The maximum level attained by any puppy was 4.48 ug/ml after 4 mg/kg tracheal lignocaine spray.

Plasma bupivacaine concentrations in children during caudal epidural analgesia.

Plasma bupivacaine concentrations were measured in 45 children, whose ages ranged from 4 months to 12 years, following administration of caudal epidural analgesia. Using 3 mg/kg of bupivacaine 0.25%, mean blood levels of 1.2-1.4 microgram/ml were reached, which are well within the limits of projected toxic levels. Simultaneous arterial and venous sampling showed a small but significant difference between these two sampling sites fo the first fifteen minutes.

Plasma lignocaine concentrations following topical laryngeal application.

Lignocaine 4%, 4 mg/kg, was sprayed onto the larynx and subglottic area of 96 children aged from 2 weeks to 12 years and plasma lignocaine concentrations were measured. While the majority were well within the accepted safe range (4.5 micrograms/ml) occasional concentrations over 8 micrograms/ml appeared in all groups. Simultaneous arterial and venous sampling showed a small but significant difference in the first 10 minutes.

Reduction of pheniramine toxicity using activated charcoal.

Pheniramine is efficiently adsorbed by Norit Medicinal Activated Charcoal in vitro. Administration of activated charcoal after pheniramine ingestion in dogs resulted in significantly lower blood levels. Norit or another proven effective activated charcoal would be of value in first-aid treatment of pheniramine poisoning.

Adsorption of halothane from a paediatric T-piece circuit by activated charcoal.

Experiments were conducted to compare the efficacy of six commonly available charcoals in adsorbing halothane in a paediatric T-piece system. Tests were also done to compare the effect of mass of charcoal and canister shape and size on adsorption and airways resistance. It was found that charcoals vary in their adsorptive capacity and that the size and shape of cannisters is important.

Phospholipid monolayers and systemic lupus erythematosus.

A hypothesis is presented of the fundamental cause of the systemic lupus erythematosus. From a study of the molecular interaction of procainamide with phospholipid monolayers, it is proposed that the drug causes phospholipid loss from the cell membrane. Chronic phospholipid loss would lead to cell lysis and antinuclear antibody production.