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Pharmacokinetics of prednisolone in man during acute and chronic exposure to high altitude

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2005-02
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Arancibia, Aquiles
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Pharmacokinetics of prednisolone in man during acute and chronic exposure to high altitude
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  • Arancibia, Aquiles;
  • Gai, María Nella;
  • Chávez Arrué, Jorge;
  • Paulos, Claudio;
  • Pinilla, E.;
  • González, C.;
  • Villanueva, S.;
  • Ritschel, W. A.;
Abstract
Introduction: The exposure to high altitude (H) produces several physiologic alterations which may induce changes in the pharmacokinetics of drugs. This hypothesis has been confirmed in previous studies which suggest that drugs which are highly bound to plasma proteins are most likely to exhibit altered pharmacokinetics. Objectives: To further elucidate the influence of H on pharmacokinetics, prednisolone was selected, since it is highly bound to plasma proteins, renally excreted and poorly bound to red blood cells. Subjects, materials and methods: Prednisolone (80 mg) was given orally to three groups of young healthy volunteers. One group was residing at sea level (L): the same volunteers were studied again after 15 hours of exposure to high altitude (3600 m, HA group), and volunteers living at H for at least six months (group HC). Results: There were no statistically significant differences in the pharmacokinetic parameters calculated from plasma data in the three situations studied. When calculated from whole blood data, however, AUC and C-max were increased and both volume of distribution and clearance diminished after exposure to H, either acute or chronically. Binding to proteins increased significantly after H exposure from 57% in group L to 75% and 94% in group H and HC, respectively. Binding to erythrocytes also increased with H exposure from 43.7% in group L to 50.6% and 61.6% in group HA and HC, respectively. The prednisolone/prednisone ratio in urine was 11.1 in group L, 7.3 in group HA and 45.6 in group HC. Conclusion: Since prednisone has very little intrinsic glucocorticoid activity and has to be converted to prednisolone for therapeutic effect, the alteration of the prednisolone/prednisone ratio, as a result of high altitude exposure could be clinically relevant. Additional experiments are desirable to further evaluate this
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URI: https://repositorio.uchile.cl/handle/2250/121048
ISSN: 0946-1965
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INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 43(2): 85-91
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