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Pharmacokinetics and Metabolism of Morphine
The pharmacokinetics of morphine significantly influence its clinical use and dosing strategies. Understanding how morphine is absorbed, distributed, metabolized, and excreted allows clinicians to tailor therapy safely and effectively.
Oral morphine undergoes extensive first-pass metabolism in the liver, resulting in reduced bioavailability compared to intravenous administration. Despite this, oral formulations remain widely used due to convenience and suitability for long-term treatment.
Morphine is metabolized primarily into morphine-3-glucuronide and morphine-6-glucuronide. Morphine-6-glucuronide contributes significantly to analgesic activity, while morphine-3-glucuronide may be associated with neurotoxic effects at high concentrations.
Renal function plays a critical role in metabolite clearance. In patients with kidney impairment, accumulation of active metabolites can increase the risk of sedation and respiratory depression. Dose adjustments and careful monitoring are essential in such cases.
Age, body composition, and concurrent medications also affect morphine pharmacokinetics. These variables underscore the importance of individualized dosing and ongoing assessment.

