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Statements Data availability statement The data used to support the findings of this study is available from the corresponding author upon request

Several factors influence tirzepatide's pharmacokinetics: Elimination pathway : Tirzepatide is primarily eliminated through proteolytic breakdown in the body, not through renal excretion Dose and duration of treatment : Higher doses and longer treatment periods result in greater drug accumulation Body weight : Body weight is a known covariate that can modestly affect drug exposure Steady-state concentrations : With weekly dosing, tirzepatide reaches steady-state levels after approximately 4 weeks of consistent administration According to FDA prescribing information, no dose adjustment is required for patients with renal impairment (including end-stage renal disease) or hepatic impairment, as these conditions do not significantly affect tirzepatide clearance

Administration of ROF for 4 days before administration of MTX significantly attenuated all these changes to normal values comparable to the control

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