Pharmacokinetics

Oral morphine is subject to extensive presystemic metabolism (mainly conjugation in gut wall and liver) and only about 20% of a dose reaches the systemic circulation; the initial oral dose is about twice the injected dose. Given s.c. (particularly) or i.m., morphine is rapidly absorbed when the circulation is normal, but in circulatory shock absorption will be delayed and morphine is best given i.v.

Morphine in the systemic circulation is metabolised by both liver and kidney; the conjugated metabolites include the pharmacologically active morphine-6-glucuronide and morphine-3-glucuro-nide.28 Elimination of morphine (10%) and metabolites is largely renal and is prolonged in renal failure, sufficient to warrant care in selecting morphine and deciding its dose and dose interval for such patients. The is 3 h (active metabolites slightly longer) and the duration of useful analgesia is 3-6 h (shorter in younger than in older subjects).

Morphine crosses the placenta and depresses respiration in the fetus at birth.

Other routes of administration used by specialists are epidural (obstetrics) and intrathecal (see p. 360); very low doses are used.

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