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- W2605621394 abstract "Altered expression and function of transporters in nonalcoholic steatohepatitis (NASH) patients may affect the pharmacokinetics (PK), efficacy, and safety of substrate drugs. A population pharmacokinetic (PopPK) analysis was performed to assess differences in morphine and morphine-3-glucuronide (M3G) disposition in NASH and healthy subjects. A total of 315 serum and 42 urine samples from 21 subjects (14 healthy; 7 NASH) were analyzed using NONMEM. Morphine and M3G PK were described by three- and one-compartment models, respectively. After accounting for the effect of total body weight on all clearance and volume of distribution parameters using an allometric scaling approach, NASH severity score (NASF; combination of fibrosis and nonalcoholic fatty liver disease activity scores) was the most significant predictor of differences in M3G exposure. The model predicted a linear decrease in the clearance of M3G with increasing NASF scores on a natural logarithmic scale. These results may provide some insight into the potential effect of NASH on the disposition of hepatic transporter substrates." @default.
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- W2605621394 date "2017-04-18" @default.
- W2605621394 modified "2023-09-27" @default.
- W2605621394 title "Population Pharmacokinetics of Morphine in Patients With Nonalcoholic Steatohepatitis (NASH) and Healthy Adults" @default.
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- W2605621394 doi "https://doi.org/10.1002/psp4.12185" @default.
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