Absorption refers to the rate and extent at which a drug leaves the site of administration. Opioids must cross at least one membrane to arrive at the site of action. Although most opi-oids are well absorbed when administered orally, subcutaneously, or intravenously, opioid onset, duration, and potency depend on numerous factors.
Lipid solubility, protein binding, ionization state, molecular size, and membrane physio-chemical properties significantly influence the absorption of opioids (Miyoshi and Leckband 2001).
Opioids are basic molecules which are highly ionized at physiologic pH. The pKa of a given opioid refers to the pH of a drug at which 50% of the drug exists in the ionized form and 50% in the nonionized form. The drugs with an increased nonionized component have an increased rate of absorption. Likewise, lipophilic opioids quickly traverse membranes compared to their hydrophilic counterparts. Smaller molecular size permits easier negotiation through membranes. The ideal opioid for absorption would be highly nonionized at physiologic pH, lipophilic, and of smaller molecular size.
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