Analysis of drug interactions in combined drug therapy by reflection method.

AIM: To set up a new method to analyze multidrug interaction in combined drug therapy.

METHODS

Based on a dose-effect curve of the combined drugs and the equieffective test, a new mathematical model was set as Q = (Eo - Et)/L (-1 < Q < 1 addition, Q < or = 1 antagonism, Q > or = 1 synergism) where Eo = an observed value (or its fitted value) of combined effect, Et = an expected value of combined effect, and L = an equieffective cutoff between Eo and Et, decided by the equieffective criterion of a special field, the number of data points, and the experimental error. The different types of experimental data were analyzed by the new model.

RESULTS

This reflection method could deal with data in combined drug therapy, unnecessary to distinguish between independent and similar action, or exclusive and non-exclusive case among drugs. The number of drugs for combination did not need to be limited. But the experimental data should be enough to fit a dose-effect curve of drugs in combination. If every dose-effect curve of drugs for combination was made, a series of Q values was obtained from all levels of dose-effect for a systematic analysis. To large animal or human experiment, the points of dose-effect of each drug used alone could be reduced to even 1 point. The results of analysis took the criterion of a special field and laboratory error into account in this method.

CONCLUSION

The reflection method is an effective method for analysis of multidrug interaction in combined drug therapy.