Comparison of cyclosporine assay methodology in the immediate postoperative period of renal transplantation.
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)
Morse
G D
GD
Department of Pharmacy, State University of New York, Buffalo 14215.
Holdsworth
M T
MT
Walshe
J J
JJ
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
D003524:Cyclosporins