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Hydrolysis of triazolam (see Scheme 19) and racemization of oxazepam (see Scheme 39) conform to this kinetic model, as shown in Figs. 8250 and 9159, respectively.

2.2.3.1.d. Pseudo-Second- and Pseudo-First-Order Reversible Reactions

When drug D reacts reversibly with A to form P according to a pseudo-second-order reaction, the rate expression for the loss of D is given by

Figure 8. Time course of formation of triazolam from its hydrolysis product (pH 2.30, 37°C). (Reproduced from Ref. 250 with permission.)

where [D] is the concentration of D at equilibrium. Equation (2.25) can be simplified to

Figure 9. Time course of racemization of oxazepam (pH 12, 0°C). (a) Racemization of /-oxazepam; (b) racemization ofd-oxazepam. (Reproduced from Ref. 159 with permission.)

where [P]„ is the concentration of product formed at equilibrium. A similar equation is derived for the case of [D], = /[A]0 and is used to describe the interaction of isoniazid and reducing sugars, as shown in Fig. 10.251

2.2.3.1.e. Pseudo-First- and Pseudo-Second-Order Reversible Reactions

Equation (2.27) represents the rate of reversible conversion of drug D to products P1 and P2. When [PJ0 = [PJ0 = 0 at t = 0, Eq. (2.27) can be integrated to give Eq. (2.28).

The loss of hydrochlorothiazide follows this model,252 although a complicated mechanism including multiple reaction steps has been proposed for its degradation.253

The loss of hydrochlorothiazide follows this model,252 although a complicated mechanism including multiple reaction steps has been proposed for its degradation.253

2.2.3.1.f. Pseudo-First-Order Consecutive Reactions

Equations (2.29) and (2.30) represent the case when drug D converts to Pb which is subsequently converted to P2 according to consecutive pseudo-fist-order reactions.

Figure 10. Time course of reaction of isoniazid with various reducing sugars under second-order reaction conditions (pH 1.8, 37°C). • , Galactose; X, lactose; O, glucose; a, maltose. (Reproduced from Ref. 251 with permission.)

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