SULPHATION/GLUCURONIDATION

    Utilizing the biochemical characteristics of paracetamol a recent study evaluated the urine paracetamol-sulfate/ paracetamol-glucuronide (PS/PG) ratio in autistic children following administration of this drug. The ratio was significantly lowered in all autistic subjects (Alberti et al, 1999). It was concluded that the inability to effectively metabolize certain compounds  toxic for the CNS, in particular phenolic amines, could exacerbate the wide spectrum of autistic behaviour.

    Paracetamol absorption is regulated by thyroid hormones, and this has long been established from pharmacological research and applications (O'Connor, 1987; Forfar, 1980; Sonne, 1993).

    Hypothyroidism leads to a decline in the clearance and metabolism of paracetamol that is mainly biotransformed by glucuronidation.  Enzymes responsible for glucuronidation in hypothyroidism are under the influence of thyroid hormones, as is the case with oxidative enzymes (Sonne, 1993).

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Alberti A, Pirrone P, Elia M, Waring RH, Romano C - "Sulphation deficit in "low-functioning" autistic children: a pilot study" Biol Psychiatry 46(3):420-4  (1999) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10435209&form=6&db=m&Dopt=r

Forfar JC, Pottage A, Toft AD, Irvine WJ, Clements JA, Prescott LF - "Paracetamol pharmacokinetics in thyroid disease" Eur J Clin Pharmacol 18(3):269-73 (1980)
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7439247&form=6&db=m&Dopt=r

O'Connor P, Feely J - "Clinical pharmacokinetics and endocrine disorders. Therapeutic implications" Clin Pharmacokinet 13(6):345-64 (1987) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3325214&form=6&db=m&Dopt=b

Sonne J - "Factors and conditions affecting the glucuronidation of oxazepam" Pharmacol Toxicol 73 Suppl 1:1-23 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8415417&form=6&db=m&Dopt=r