Influence of demographic factors on cyclosporine pharmacokinetics in adult uremic patients.
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 FSR = FWR: FSR = 43.2 +/- 21.7%; FWR = 43.5 +/- 18.5%; FWH = 36.4 +/- 17.3%; CLSR = 849 +/- 363 ml/min; CLWR = 380 +/- 156 ml/min; CLWH = 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 CLWH but not CLSR or CLWR. 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.
Grevel
J
J
Department of Surgery, University of Texas Medical School, Houston 77030.
Reynolds
K L
KL
Rutzky
L P
LP
Kahan
B D
BD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001682:Biological Availability; D001827:Body Height; D001835:Body Weight; D003524:Cyclosporins / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014511:Uremia / Q000378:metabolism*
D003524:Cyclosporins; D000410:Alanine Transaminase