Correlation of kinetic parameters and thermal behavior of segmented polyurethane elastomers with biological responses
✍ Scribed by G. W. C. Hung; L. J. Nunez; J. Autian
- Publisher
- John Wiley and Sons
- Year
- 1975
- Tongue
- English
- Weight
- 693 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
minophen following oral administration of equivalent doses of pacetaminophenyl decanoate. The availability of drug from this ester form was 34% of that produced by acetaminophen. Concomitant administration of p-acetamidophenyl decanoate, pancreatic lipase (3 Wilson units/mg), and calcium chloride increased the availability from 34 to 73% as calculated from the data reported in Table .
To investigate the feasibility of using a combination of ester derivatives with pancreatic lipase and calcium ions to achieve a prolonged release of acetaminophen, p-acetamidophenyl acetate and p-acetamidophenyl dodecanoate, equivalent to 20 and 40 mg/kg of acetaminophen, respectively, were administered with 59 mgbg of pancreatic lipase and 10 mg/kg of calcium carbonate. The acetate ester was included to provide the initial release, and the dodecanoate ester was selected because of its slower hydrolysis rate. The amounts of pancreatic lipase and calcium carbonate were determined to be adequate from preliminary studies.
The results of this combination using a short chain ester and an intermediate ester are shown in Table VI and in Fig. . At the 1-, 3-, and 5-hr intervals, the blood concentrations were somewhat higher than an average of 21 Ng/ml; a t 7 and 10 hr, they were slightly below. The control used in this study was identical to the experiment, except that the pancreatic lipase used in the dose was inactivated by moisture and heat. No statistical difference at a 90% confidence level was noted at the 1-and 3-hr intervals; however, a t 5-, 7-, lo-, and 13-hr intervals, a significant difference was observed. The hydrolysis and subsequent absorption from p-acetamidophenyl dodecanoate were facilitated by the inclusion of lipase in the dose. The availability of acetaminophen was increased by a factor of 1.7 when the combination included the active enzyme preparation.