The kinetics of "C-labelled morphine and pethidine were studied by positron emission tomography (PET) at different levels of the spinal canal (C4, T4, T5, T6, L1 and L6). Studies were performed in the Rhesus monkey after intrathecal and extradural administration of the drugs at the lumbar level (L3-L4 or L+L5, seven experiments). Radioactivity 100-300 times higher than with even distribution in the body was measured initially near the site of injection for both morphine and pethidine, irrespective of the route of administration. After injection of pethidine, high activity was observed at the L6 and L1 levels, whilst the radioactive uptake was lower at T6 ( 10-20y0 of those at lumbar level). Morphine-derived "C-radioactivity showed more constant levels along the spinal canal, except at C4 where radioactivity was low. In CSE' taken from the cervical level the peaks of radioactivity of the two drugs appeared 80-1 70 min after injection. The importance of different distribution routes was quantified in a pharmacokinetic coinpartment model, using the above results. The systemic distribution was extensive, irrespective of drug or route of administration. From the site of injection the systemic distribution was at least 60 times larger than the rostra1 distribution within the spinal canal.
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