Blood cyclosporine pharmacokinetics in patients undergoing marrow transplantation: Influence of age, obesity, and hematocrit

Gary C. Yee, Timothy R. McGuire, Dennis J. Gmur, Thomas P. Lennon, H. Joachim Deeg

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Blood cyclosporine pharmacokinetics were studied in 85 patients aged 1-52 (median: 22) years undergoing allogeneic bone marrow transplantation for the treatment of hematologic disease. Pharmacokinetic studies were carried out during the first two weeks posttransplant after an intravenous dose of 2.1—4.4 mg/kg. Whole-blood cyclosporine concentrations were measured by high-performance liquid chromatography. Multiple stepwise regression analysis indicated that age (P<0.001) and hematocrit (P<0.05) correlated with cyclosporine clearance (CL) while steady-state volume of distribution (V„) did not correlate with any of the factors studied. Cyclosporine CL significantly differed among nonobese patients in different age groups; patients <10 years old had a higher mean CL (13.1 ml/min/kg) than patients 11-20, 21-30, 31-40, or >40 years old (mean CL: 8.5—10.3 ml/min/kg) (P<0.05). No significant differences in cyclosporine CL and V„ were observed between obese (>125% ideal body weight) patients and age-matched nonobese patients. Hematocrit values (range: 24—39) were inversely correlated with cyclosporine CL, which suggests that red blood cells function as important ligands in cyclosporine binding. These results show that blood cyclosporine CL is higher in marrow transplant recipients than in solid organ transplant recipients and that these differences may be related to lower hematocrits in marrow transplant recipients compared with solid organ transplant recipients. When compared with previously published serum cyclosporine CL data, our findings suggest that age-related changes in CL are primarily related to changes in plasma protein binding and that obesity does not significantly alter cyclosporine CL and Vss.

Original languageEnglish (US)
Pages (from-to)399-402
Number of pages4
JournalTransplantation
Volume46
Issue number3
DOIs
StatePublished - Sep 1988

ASJC Scopus subject areas

  • Transplantation

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