Ch

carmethizole

Scheme 68. Consecutive loss of carbamate groups in carmethizole (NSC-602668). The reactivity of one carbamate group is greater than that of the other. (Reproduced from Ref. 46 with permission.)

A good example of consecutive reactions is the degradation of carmethizole (NSC-602668), an experimental cytotoxic agent (Scheme 68).44 The hydrolysis of hydrocortisone hemisuccinate (Fig. 11)30 and alkaline epimerization followed by hydrolysis of etoposide (Fig. 12)156 157 fit this mathematical model even though their degradation pathways are more complex.

2.2.3.1.g. Pseudo-First-Order Reversible and Consecutive Reactions

When drug D is reversibly converted to P1, which is reversibly converted to P2 by apparent first-order kinetics, Equations (2.31) and (2.32) represent the rate and integrated expressions, respectively.

hydrocortisone hemisuccinate hydrocortisone hemisuccinate

Figure 11. Time course of hydrolysis of hydrocortisone hemisuccinate (pH 6.9, 70°C). (Reproduced from Ref. 30 with permission.)

Figure 11. Time course of hydrolysis of hydrocortisone hemisuccinate (pH 6.9, 70°C). (Reproduced from Ref. 30 with permission.)

Figure 12. Time courses of epimerization and hydrolysis of etoposide (pH 10, 37°C). (Reproduced from Ref. 157 with permission.)

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