Multiple sequence studies

For the first time, a systematic uniform ab initio study of endohedral complexes of C60, Si60 and Ge60 with monoatomic cations (Li+, Na+, K+ and Rb+) and anions (F-, Cl% Br and P) was performed. The 3-21 G level (3-21+G for the anions) was used. This could be achieved by application of the multiplicative integral approximation [86], as implemented in the program BRABO [87]. The sequence studied for the cages bears a close resemblance with isomorphic substitution in zeolites modifying its catalytic activity via bridging hydroxyls. 

There are also other BE-type assessments. Interaction studies assess the influence on bioavailability by other individual factors, such as food, alcohol, or other drugs. Such studies are usually single-sequence crossover, but the assessment method remains the same—whether confidence intervals of AUC and Cmax ratios fall within (0.80, 1.25). The same can be said of PK similarity assessments between subject populations, for example, healthy volunteers versus patients. The assessment method is the same as that used for BE, but important differences remain. In typical BE studies, subjects are densely sampled so that individual PK parameters, AUC and Cmax, can be determined with precision. PK similarity assessments are concerned with the differences in different populations, instead of formulations. The assessments are usually based on multiple (parallel) studies, as crossover studies are not possible, and sequence and period effects are not considered. Assessments involve obtaining estimates of average PK parameters in the populations and the 90% confidence intervals for the ratios of the average PK parameters. 

Ovcharenko, I., Loots, G. G., Giardine, B. M., et al. (2005) Mulan multiple-sequence local alignment and visualization for studying function and evolution. Genome Res. 15, 184-194. 

---