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Influence of Demographic Factors on Cyclosporine Pharmacokinetics in Adult Uremic Patients
Author(s) -
Grevel Joachim,
Reynolds Kimberley L.,
Rutzky Lynn P.,
Kahan Barry D.
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03324.x
Subject(s) - radioimmunoassay , pharmacokinetics , chemistry , medicine , alanine transaminase , endocrinology , aspartate transaminase , hemoglobin , hematocrit , bioavailability , bilirubin , triglyceride , alkaline phosphatase , cholesterol , pharmacology , biochemistry , enzyme
The causes of variability in cyclosporine (CS) clearance (CL) are mostly unknown. The pharmacokinetics of CS were studied in 30 adult uremic patients after single intravenous and oral doses by analyzing serial concentrations in serum by radioimmunoassay (SR) and in whole blood by radioimmunoassay (WR) and high pressure liquid chromatography (WH). Bioavailability (F) and CL were calculated by noncompartmental models and were significantly different depending upon the assay method except for F SR = F WR : F SR = 43.2 ± 21.7%; F WR = 43.5 ± 18.5%; F WH = 36.4 ± 17.3%; CL SR = 849 ± 363 ml/min; CL WR = 380 ± 156 ml/min; CL WH = 559 ± 174 ml/min. The age of the patients and parameters describing body size such as weight, surface area and percent of ideal weight were not correlated with CL. The height of the patients correlated with CL WH but not CL SR or CL WR . Parameters responsible for CS binding in blood such as cholesterol, triglyceride, hemoglobin concentration or hematocrit did not explain variability in CL. Of the factors indicative of liver function alanine transaminase activity but not aspartate transaminase, lactate dehydrogenase, alkaline phosphatase activity nor total bilirubin concentration in serum was correlated with CL. F was not correlated with any of the demographic factors except for alanine transaminase. None of the significant correlations explained enough of the variability to afford a reliable prediction of CL or F.