title: Comparison of cyclosporine assay methodology in the immediate postoperative period of renal transplantation.
abstract: The method of measurement of cyclosporine concentrations in renal transplant recipients varies between centers and employs either high-performance liquid chromatography (HPLC) or radioimmunoassay (RIA). The merit of using HPLC for identifying the parent compound versus the RIA technique, which also measures certain cross-reactive metabolites that accumulate during renal impairment, is controversial. As a result of the lack of uniformity among centers, an abundance of complex literature that describes the disposition of this potent immunosuppressive agent, as well as a wide range of guidelines for therapeutic monitoring, has evolved. To examine the influence of assay methodology on the repeated determination of cyclosporine in the immediate postoperative period, a time when renal function is often unstable, eight renal transplant recipients were studied after i.v. and oral administration on up to four separate occasions. Whole-blood samples were analyzed by HPLC and RIA. Intravenous kinetic analysis yielded a mean total body clearance of 0.24 +/- 0.2 L/min (RIA) and 0.31 +/- 0.1 L/min (HPLC) (p greater than 0.05), the mean volume of distribution was 2.17 +/- 0.6 L/kg (RIA) and 2.75 +/- 1.2 L/kg (HPLC) (p greater than 0.05), and a mean half-life was 11.7 +/- 4.4 h (RIA) and 12.8 +/- 3.8 h (HPLC) (p greater than 0.05). The mean bioavailability was 0.36 +/- 0.23 (RIA) and 0.28 +/- 0.15 (HPLC) (p greater than 0.05). Regression of the 12-h cyclosporine (RIA versus HPLC) concentration yielded a line described by the following equation: RIA = 72 + 1.6 (HPLC).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacy, State University of New York, Buffalo 14215.
authors.forename: G D
authors.initials: GD
authors.lastname: Morse
authors.forename: M T
authors.initials: MT
authors.lastname: Holdsworth
authors.forename: J J
authors.initials: JJ
authors.lastname: Walshe
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000097:blood* / Q000493:pharmacokinetics; D006084:Graft Rejection; D006801:Humans; D007275:Injections, Intravenous; D016030:Kidney Transplantation; D011863:Radioimmunoassay; D014184:Transplantation, Homologous
chemical_list: D003524:Cyclosporins