Microdialysis of triamcinolone acetonide in rat muscle

Authors

  • Cioli Rojas,

    1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610
    Current affiliation:
    1. Faculty of Pharmacy, Central University of Venezuela at Caracas, Caracas, Venezuela.
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  • Nelamangala V. Nagaraja,

    1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610
    Current affiliation:
    1. Clinical Discovery, Bristol-Myers Squibb Company, Princeton, NJ 08543.
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  • Alistair I. Webb,

    1. Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32610
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  • Hartmut Derendorf

    Corresponding author
    1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610
    • Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610. Telephone: 352-846-2726; Fax: 352-392-4447
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Abstract

The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V. bolus 50 mg/kg of the phosphate ester of TA (TAP) followed by 23 mg/kg/h infusion. In vivo recovery was calculated by retrodialysis. The concentration determined at steady state in microdialysate, corrected for recovery, was 2.73 ± 0.42 μg/mL compared to 21.9 ± 2.3 μg/mL in plasma. The pharmacokinetics of TA in plasma was described by an open two-compartment model with a terminal half-life of 2.7 h. The clearance of TA in rats determined by compartmental analysis was 0.94 L/h/kg. The measured microdialysate levels of TA in muscle, corrected for recovery, were comparable to the predicted free drug levels in the peripheral compartment. Protein binding in rat plasma, measured by ultrafiltration, was 90.1%. The microdialysis in vivo recovery in muscle was similar to the in vitro recovery under stirred conditions. The results show the applicability of microdialysis to measure free tissue concentrations of TA in rats. © 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:394–397, 2003

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