Kinetics of absorption of a new once-a-day formulation of theophylline in the presence and absence of food.

Two three-way crossover studies were done to characterize the drug release characteristics of Monospan (3M Pharmaceuticals, St. Paul, MN) capsules, a new once-a-day theophylline formulation. In the first study, 22 healthy males received single 450-mg doses of Monospan in the presence and absence of a high-fat breakfast; the same dose of Somophyllin (Fisons, Rochester, NY) immediate-release liquid was given to fasted subjects as a reference. The second study involved 29 healthy males given a single dose of 900 mg of Monospan in the presence and absence of the same high-fat meal; Theo-24 (G. D. Searle and Co., Skokie, IL) capsules were given to fasted subjects as a reference. The results of both studies showed that food did not affect the absorption of theophylline from Monospan; peak concentration, to and area under the serum concentration-time curve were all unchanged. The absorption rates were similar with both strengths and dietary conditions and showed that theophylline was absorbed slowly from Monospan at a constant rate (approximately 3.2%/h) over 24 h. Absorption continued past 24 h, and the extent of absorption from Monospan compared with that from each reference averaged 88% or higher. A good correlation (r > 0.980) was observed for Monospan between the amount absorbed in vivo and the amount released in the in vitro dissolution test, a result that demonstrates the precise rate control of Monospan. We conclude that Monospan is a suitable once-a-day formulation that can be taken without regard to food.

Factors influencing the reproductive decision after genetic counseling.

Here we report a follow-up study involving interviews with 164 couples 2-3 years after genetic counseling to assess the influence of various factors on their reproductive planning. The results show that the desire to have children and the absence of personal experience with the disorder (no close relative being affected) are important single factors for the decision to opt for having children after genetic counseling. The magnitude of the genetic risk is of relative importance in reproductive planning. Seventy percent of the couples with a high genetic risk (greater than 15%) opted for having children. When the disorder was perceived as severe and the risk was interpreted as high, 72% opted for having children. The availability of prenatal diagnosis became important only in combination with a high genetic risk (greater than 15%). Forty-seven percent of the couples with a high genetic risk refrained from having children when prenatal diagnosis was not available. In the absence of prenatal diagnosis, couples who had an affected child were more cautious about trying again than those who did not--50% versus 14% decided to abstain. This study has provided some insight into the complexity of reproductive decision-making after genetic counseling. The findings may help genetic counselors and clinical geneticists understand and support counselees in their decision-making process, which is "multi-factorial."

Kinetics and mechanism of degradation of cefotaxime sodium in aqueous solution.

The degradation kinetics and mechanism of a potent new cephalosporin, cefotaxime sodium, in aqueous solution were investigated at pH 0-10 at 25 degrees and an ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo first-order kinetics with respect to cefotaxime sodium concentration. The data suggested that the rate of degradation was influenced significantly by solvolytic, hydrogen ion, and hydroxide ion catalysis. No primary salt effects were observed in the acid or neutral regions; however, a positive salt effect was observed at pH 8.94. Buffer catalysis due to the buffer species employed was not seen during the kinetic studies. The pH-rate profile at 25 degrees indicated that the maximum stability of cefotaxime sodium occurred in the pH 4.5-6.5 region. In aqueous solution, cefotaxime was shown to degrade by two parallel reactions: de-esterification at the C-3 position and beta-lactam cleavage. Good agreement between the theoretical pH-rate profile and the experimental data support the proposed degradation process.