Paracetamol Clinical Trial
Official title:
A Single Centre Prospective Randomised Study to Investigate the Cerebrospinal Fluid (CSF) Pharmacokinetics of Intravenous Paracetamol in Humans
Despite its use for decades all over the world, the exact mechanism of action of paracetamol
is not fully understood and essentially involves a combination of hypotheses. It is known to
have an effect via the central nervous system, and of the many mechanisms proposed, one
hypothesis is that it may have indirectly activate CB1 (cannabinoid) receptors, through its
novel metabolite AM404.
This study aims to elucidate cerebrospinal levels of paracetamol and to measure the
concentration of its metabolites, including AM404 in CSF. This may, in turn, give us useful
information on the mechanism of action of paracetamol.
Patients undergoing spinal blockade for urological surgery were administered 1g paracetamol
intravenously at varying intervals prior to spinal anaesthesia, at which time 5mls of
cerebrospinal fluid and 10mls of blood were sampled, and analysed for concentrations of
paracetamol, paracetamol glucuronide, paracetamol sulphate, and AM404, a known
endocannabinoid reuptake inhibitor, and metabolite of paracetamol.
Paracetamol readily penetrates into the cerebrospinal fluid in animal studies and in
children. This could account for the rapid central analgesic and antipyretic action of
intravenous paracetamol however this remains to be studied in adults. AM404 has never before
been identified in humans, and its presence in CSF following paracetamol supports the
hypothesis of a central mechanism of action of paracetamol via AM404.
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Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
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