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Pharmacokinetics of Troglitazone in Patients with Renal Insufficiency

  • Clinical Pharmacokinetics
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Abstract

Objective: The pharmacokinetic profiles of troglitazone and two metabolites were evaluated following a single 400mg oral dose of troglitazone in 20 patients with various degrees of renal function.

Methods: Plasma troglitazone and metabolite concentrations were determined by high performance liquid chromatography, and troglitazone free fraction was determined by ultracentrifugation.

Results: Mean maximum plasma concentration and area under the curve for total troglitazone appeared lower in patients with severe renal impairment (SRI) compared with those with normal renal function (NRF). Troglitazone free fraction was higher in patients with SRI (4.85%) than in subjects with NRF (1.66%), producing similar exposure values for unbound troglitazone, the moiety presumed to exert the pharmacological effect. Regression analysis revealed poor correlations of creatinine clearance value with total troglitazone, unbound troglitazone, and metabolite pharmacokinetic parameter values.

Conclusion: These data indicated that renal function does not predict troglitazone pharmacokinetics and systemic exposure to unbound troglitazone is unaltered with renal impairment. Thus, troglitazone dose adjustment based on pharmacokinetics is not required in patients with renal insufficiency.

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Authors and Affiliations

  1. Department of Pharmacokinetics and Drug Metabolism, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan, 48105, USA

    Philip W. Knowlton, Cho-Ming Loi, Joanne I. Brodfuehrer, Edward J. Randinitis &  Jeffrey R. Koup

  2. Department of Clinical Pharmacology, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan, USA

    Artemios B. Vassos & Allen J. Sedman

  3. Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York, USA

    Robert A. Blum

Authors
  1. Philip W. Knowlton
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  2. Cho-Ming Loi
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  3. Artemios B. Vassos
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  4. Robert A. Blum
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  5. Joanne I. Brodfuehrer
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  6. Edward J. Randinitis
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  7. Allen J. Sedman
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  8. Jeffrey R. Koup
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Knowlton, P.W., Loi, CM., Vassos, A.B. et al. Pharmacokinetics of Troglitazone in Patients with Renal Insufficiency. Clin. Drug Investig. 17, 127–136 (1999). https://doi.org/10.2165/00044011-199917020-00007

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  • DOI: https://doi.org/10.2165/00044011-199917020-00007

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