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By Thomas F. Woolf

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261, these authors then used the relations of AUC and CL in Eq. ( I ? , constant clearance) for parent drug and metabolite relative to changes in dose and time. Equation (29) is applicable to any route of administration, but does require that the route used for the single-dose measurements of AUC be the same as that to be employed for steady-state measurements of concentrations. This requirement usually ensures that availabilities of the parent drug and metabolite formed are the same between single and chronic doses.

2 mg) administration of morphine in humans on the profile of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G). The common terminal half-life observed for parent drug and both metabolites shown for the slow-release buccal formulation are longer than obtained after the immediate-release dosage form, suggestive of absorption being rate-limiting. (From Ref. ) 18 Smith +other) A ------+ Other elimination pathways k, F = k a ( f a FH) A Scheme 4 f;CL F(m) Absorption of drug, metabolism to a primary metabolite uith first-pass formation of metabolite followed by excretion or metabolism.

29) can be rearranged and written more simply as, where AUC(m) is determined after a single dose of parent drug. Under these conditions of regular dosing to steady state, data on the disposition of the parent drug is not necessarily required when estimating C(m),,,,,,, although most often the parent drug data are available. When a single intravenous bolus dose of parent drug was used to obtain measurement of AUC(m), but then a continuous infusion of rate R,, is later employed, one can also derive C(m),, ‘,\c without complete knowledge of the disposition of parent drug.

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