Yiy2yi [p1 [d0[d[p2

expCyji) +

YiY2

YiY2 (YI~Y2)YI

where

2.2.3.1.h. Pseudo-First-Order Parallel Reactions k2 k1 P, <T- D P,

Equations (2.33) and (2.34) pertain when drug D converts to Pi and P2 via independent first-order pathways.

Equations (2.33) and (2.34) pertain when drug D converts to Pi and P2 via independent first-order pathways.

Many drugs degrade to more than one product so this scheme is quite common. Often, more than two products are formed.

2.2.3.1.i. Pseudo-First-Order Reversible and Parallel Reactions

When both Pi and P2 are capable of being converted back to D, Eqs. (2.35) and (2.36) adequately describe the kinetics.

where

Degradation of pilocarpine in the neutral pH region appears to conform to this model (Fig. 1 3).254 Technically, however, isopilocarpine can also degrade to isopilocarpic acid; therefore, a more complete scheme for the degradation of polocarpine is

However, within the limits of the experimental conditions, this more complex scheme reduces to that defined by Eq. (2.35).

2.2.3.1.j. Pseudo-First- and Psuedo-Second-Order Reversible and Parallel Reactions k

A reaction pathway similar to, but more complicated than, that considered above is one in which the conversion of D to Pi and P2 is reversible. Epimerization and hydrolysis of hetacillin apparently conform to this model, as shown in Fig. 14,163 even though epihetacillin can also dissociate and the isomerization of hetacillin to epihetacillin should be considered reversible.

2.2.3.1.k. Pseudo-First-Order Parallel and Consecutive Reactions k, ki k3 P, D P, P,

When Pi subsequently converts to P3 according to a first-order reaction in a pseudofirst-order parallel reaction, Eqs. (2.37) and (2.38) represent the rate and integrated expressions, respectively.

Figure 13. Time course of degradation of pilocarpine (pH 6.0, 80°C). (Reproduced from Ref. 254 with permission.)
Figure 14. Time courses of epimerization and hydrolysis of hetacillin (pD 10.6, 35°C). (Reproduced from Ref. 163 with permission.)

The alkaline degradation of cefixime255 and pilocarpine38 appears to conform to this model, even though the actual pathways/mechanisms may be more complex than indicated by this scheme.

2.2.3.1.1. Pseudo-First-Order Reversible, Parallel and Consecutive Reactions

When Pi is in equilibrium with D, Eqs. (2.39) and (2.40) can describe this model.

Y1-Y2

Y1-Y2 Y1-Y2

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