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Effect of P-glycoprotein inhibitors erythromycin and cyclosporin A on brain pharmacokinetics of nimodipine in rats

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Summary

Effect of P-glycoprotein (P-gp) inhibitors erythromycin (Ery) and cyclosporin A(CsA) on brain pharmacokinetics of nimodipine (NMD) in rats was studied. NMD concentrations in rat plasma and brain were determined after iv 2 mg/kg NMD alone, coadministration with Ery and CsA, respectively. It was found that concentrations of NMD in plasma of the three groups had a little difference, but brain concentrations of NMD in rats co-administrated with Ery and CsA were significantly higher than those in rats NMD alone. Significances of NMD in rat brain were found at 20, 40, 60 and 90 min after iv NMD. The brain T1/2 in rat treated with ery(75.0 min) and CsA(79.0 min) were larger than that(44.2 min) in rats NMD alone. The results indicated that P-gp inhibitors Ery and CsA may increase concentration in rat brain by inhibiting elimination of NMD from brain.

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Authors and Affiliations

  1. Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 210009, Nanjning, People’s of Republic of China

    X. D Liu, L. Zhang & L. Xie

Authors
  1. X. D Liu
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  2. L. Zhang
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  3. L. Xie
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The project supported by the Key Laboratory of Jiangsu Drug Metabolism and Pharmacokinetics and the Education Commission Foundation of Jiangsu, PRC.

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Liu, X.D., Zhang, L. & Xie, L. Effect of P-glycoprotein inhibitors erythromycin and cyclosporin A on brain pharmacokinetics of nimodipine in rats. European Journal of Drug Metabolism and Pharmacokinetics 28, 309–313 (2003). https://doi.org/10.1007/BF03220184

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  • DOI: https://doi.org/10.1007/BF03220184

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