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Glucuronidation and sulphation of paracetamol in HIV‐positive patients and patients with AIDS
Author(s) -
O’Neil,
Pezzullo,
Di Girolamo,
Tsoukas,
Gabriel Wainer
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00084.x
Subject(s) - glucuronidation , sulfation , pharmacology , zidovudine , medicine , population , concomitant , metabolite , acetaminophen , chemistry , human immunodeficiency virus (hiv) , immunology , biochemistry , microsome , viral disease , environmental health , enzyme
Aims To gauge the effect of disease state and disease progression on the glucuronidation and sulphation of paracetamol (APAP) among HIV‐positive patients and patients with AIDS.Methods The extent of APAP glucuronidation and APAP sulphation was assessed using a spot urine sample collected 4 h after the oral administration of 500 mg of APAP to 108 patients with AIDS or HIV infection. The molar concentrations of APAP and its glucuronide and sulphate metabolites were determined using a validated h.p.l.c. method and glucuronidation and sulphation indices were constructed using APAP metabolite/APAP molar concentration ratios.Results No effect of disease state, AIDS vs asymptomatic HIV positive vs control, on APAP glucuronidation or sulphation was observed. The patient population was studied over time and disease progression also did not significantly alter the calculated glucuronidation and sulphation indices. The effect of the concomitant administration of other therapeutic agents was assessed and in the cross sectional portion of the study dapsone appeared to significantly decrease APAP sulphation as did lamivudine. In the longitudinal portion of the study the latter effect was not observed but zidovudine was seen to increase APAP glucuronidation. The data also indicates that APAP glucuronidation may be reduced in patients who are >10% below their ideal body weight.