calculate the degree of ionisation of codeine (shown below), in the stomach ( $\mathrm{pH}=2)$ and the intestine $(\mathrm{pH}=8)$. With regards to the ADME process, describe how the degree of ionisation of codeine will affect its absorption in the stomach and the intestine

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∻Solution∻ ‖ 1 ⋮ **Identify the reaction**: Codeine is a weak base, and its degree of ionization depends on the pH of the environment. The ionization can be described by the Henderson-Hasselbalch equation: $ ext{pH} = ext{pKa} + \log \left( \frac{[ ext{Base}]}{[ ext{Acid}]} ight) $. ‖‖ 2 ⋮ **Determine the pKa of codeine**: The pKa of codeine is approximately 8.2. ‖‖ 3 ⋮ **Calculate the degree of ionization in the stomach**: At pH 2, the degree of ionization can be calculated using the Henderson-Hasselbalch equation: $ ext{pH} = ext{pKa} + \log \left( \frac{[ ext{Base}]}{[ ext{Acid}]} ight) $. Rearranging for the ratio of base to acid: $ \frac{[ ext{Base}]}{[ ext{Acid}]} = 10^{ ext{pH} - ext{pKa}} = 10^{2 - 8.2} = 10^{-6.2} $. This indicates that codeine is mostly in its ionized form in the stomach. ‖‖ 4 ⋮ **Calculate the degree of ionization in the intestine**: At pH 8, the degree of ionization can be calculated similarly: $ \frac{[ ext{Base}]}{[ ext{Acid}]} = 10^{8 - 8.2} = 10^{-0.2} \approx 0.63 $. This indicates that codeine is less ionized in the intestine. ‖‖ 5 ⋮ **Impact on absorption**: The degree of ionization affects the absorption of codeine. Non-ionized (neutral) molecules are more lipophilic and can cross cell membranes more easily. Therefore, codeine is better absorbed in the intestine where it is less ionized. ‖ ∻Answer∻ ⚹ Codeine is mostly ionized in the stomach (pH 2) and less ionized in the intestine (pH 8). It is better absorbed in the intestine due to its lower degree of ionization. ⚹ ∻Key Concept∻ ⚹ Degree of ionization affects drug absorption ⚹ ∻Explanation∻ ⚹ Non-ionized molecules are more lipophilic and can cross cell membranes more easily, leading to better absorption in the intestine where codeine is less ionized. ⚹◊How does the degree of ionization of codeine change between pH 2 and pH 8, and how does this impact absorption in the stomach and intestine?⍭ Generate me a similar question◊

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