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The aim of the present study was to perform an in vivo estimation of the Michaelis-Menten constants of the major metabolic pathways of paracetamol (APAP).

A two-occasion, single-dose cross-over trial was performed using 60 and 90 mg/kg doses of APAP in healthy patients undergoing third molar dental extraction. Plasma samples were collected over 24 h and urine was collected for 8 h after dosing. Twenty patients were enrolled in the study and complete data for plasma and urine were available for both doses for 13 volunteers who were included in the analysis; seven of the volunteers were men, the median age (range) was 22 years (19–31) and the median weight (range) was 68 kg (50–86).

The mean (95% CI) km for APAP glucuronidation was 6.89 mmol/L (3.57–10.22) and the Vmax was 0.97 mmol/h per kg (0.65–1.28). The km for APAP sulphation was 0.097 mmol/L (0.041–0.152) and the Vmax was 0.011 mmol/h per kg (0.009–0.013). For the combined excretion of APAP-cysteine and APAP-mercapturate, the km was 0.303 mmol/L (0.131–0.475) and the Vmax was 0.004 mmol/h per kg (0.002–0.005).

The estimates for in vivo Michaelis-Menten constants for APAP glucuronidation and sulphation were in the order of those reported previously using in vitro methods.
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Keywords: Michaelis-Menten; glucuronidation; metabolism; paracetamol; sulphation

Document Type: Research Article

Publication date: January 1, 2009

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