TY - JOUR
T1 - Effects of oral contraceptive steroids on acetaminophen metabolism and elimination
AU - Mitchell, Mack C.
AU - Hanew, Teruki
AU - Meredith, Christopher G.
AU - Schenker, Steven
PY - 1983/7
Y1 - 1983/7
N2 - Plasma acetaminophen elimination was examined in women taking low-dose estrogen oral contraceptive (OC) steroids and in age-matched control women. Fractional rates of elimination and fractional clearances were calculated for each of the metabolic pathways, including oxidation, sulfation, and glucuronidation. The cysteine adduct and mercapturic acid derivative of acetaminophen were used as an index of oxidative biotransformation, a potentially toxic route of metabolism for acetaminophen. Plasma acetaminophen clearance rose from 287 ± 13 ml/min to 470 ± 51 mllmin in women taking OC steroids, whereas elimination t 1 2 decreased from 2.40 ± 0.14 hr to 1.67 ± 0.16 hr. The fractional clearance and rate of elimination of acetaminophen by glucuronidation increased in women taking OC steroids, whereas the clearance and elimination by sulfation did not differ significantly from values in control subjects. Fractional clearance of the cysteine adduct also increased significantly, but clearance of acetaminophen mercapturic acid did not change. These data suggest that the increased clearance of acetaminophen from plasma in women taking OC steroids results from increased glucuronidation of the drug, although the mechanism is not known.
AB - Plasma acetaminophen elimination was examined in women taking low-dose estrogen oral contraceptive (OC) steroids and in age-matched control women. Fractional rates of elimination and fractional clearances were calculated for each of the metabolic pathways, including oxidation, sulfation, and glucuronidation. The cysteine adduct and mercapturic acid derivative of acetaminophen were used as an index of oxidative biotransformation, a potentially toxic route of metabolism for acetaminophen. Plasma acetaminophen clearance rose from 287 ± 13 ml/min to 470 ± 51 mllmin in women taking OC steroids, whereas elimination t 1 2 decreased from 2.40 ± 0.14 hr to 1.67 ± 0.16 hr. The fractional clearance and rate of elimination of acetaminophen by glucuronidation increased in women taking OC steroids, whereas the clearance and elimination by sulfation did not differ significantly from values in control subjects. Fractional clearance of the cysteine adduct also increased significantly, but clearance of acetaminophen mercapturic acid did not change. These data suggest that the increased clearance of acetaminophen from plasma in women taking OC steroids results from increased glucuronidation of the drug, although the mechanism is not known.
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U2 - 10.1038/clpt.1983.127
DO - 10.1038/clpt.1983.127
M3 - Article
C2 - 6861437
AN - SCOPUS:0020530194
SN - 0009-9236
VL - 34
SP - 48
EP - 53
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 1
ER -