AIMS: The capacity for sulphation of phenols appears to be impaired in the colonic mucosa of patients with ulcerative colitis. The aim of the present study was to investigate the systemic capacity for sulphation of phenols in patients with ulcerative colitis assessed by the metabolic clearances of paracetamol to the sulphate, glucuronide and glutathione derived metabolites. METHODS: Ten patients with ulcerative colitis and 10 control subjects received a single oral dose of paracetamol (1 g). Venous blood samples were collected frequently for pharmacokinetic determinations (one compartment model). Urine was collected for 24 h. Plasma samples were analysed for parent drug and urine samples for parent drug and metabolites by h.p.l.c. Partial metabolic clearances were calculated as the fractional urinary recovery of each conjugate multiplied by the apparent oral clearance of paracetamol. RESULTS: The apparent oral clearance of paracetamol and the partial clearances of its metabolites were not significantly different between the two study groups. Median value and the corresponding 25th and 75th percentiles for the clearance of the sulphate metabolites were 93.6 (82.5-138.8) ml kg(-1)h(-1) and 77.4 (75.5-99.1), patients with ulcerative colitis and control subjects, respectively. CONCLUSIONS: These results do not indicate a general impairment of the systemic capacity for sulphation of paracetamol in patients with ulcerative colitis.
AIMS: The capacity for sulphation of phenols appears to be impaired in the colonic mucosa of patients with ulcerative colitis. The aim of the present study was to investigate the systemic capacity for sulphation of phenols in patients with ulcerative colitis assessed by the metabolic clearances of paracetamol to the sulphate, glucuronide and glutathione derived metabolites. METHODS: Ten patients with ulcerative colitis and 10 control subjects received a single oral dose of paracetamol (1 g). Venous blood samples were collected frequently for pharmacokinetic determinations (one compartment model). Urine was collected for 24 h. Plasma samples were analysed for parent drug and urine samples for parent drug and metabolites by h.p.l.c. Partial metabolic clearances were calculated as the fractional urinary recovery of each conjugate multiplied by the apparent oral clearance of paracetamol. RESULTS: The apparent oral clearance of paracetamol and the partial clearances of its metabolites were not significantly different between the two study groups. Median value and the corresponding 25th and 75th percentiles for the clearance of the sulphate metabolites were 93.6 (82.5-138.8) ml kg(-1)h(-1) and 77.4 (75.5-99.1), patients with ulcerative colitis and control subjects, respectively. CONCLUSIONS: These results do not indicate a general impairment of the systemic capacity for sulphation of paracetamol in patients with ulcerative colitis.
Authors: Caroline D van der Marel; Brian J Anderson; Richard A van Lingen; Nicholas H G Holford; Marien A L Pluim; Frank G A Jansman; John N van den Anker; Dick Tibboel Journal: Eur J Clin Pharmacol Date: 2003-05-22 Impact factor: 2.953