Pharmacokinetics and nephrotoxicity of cyclosporine in renal transplant recipients.

Pharmacokinetics of Cyclosporine (CsA) were studied in 14 renal transplant patients during a three-month period of treatment. At 3 and 15 days after transplantation 12-hr blood level studies of the drug were performed to calculate the elimination half-life, area under the curve (AUC), and total blood clearance; trough levels were measured twice weekly. In 9 patients terminal half-lives could be calculated after discontinuation of CsA treatment. In the course of CsA treatment, prolongation of half-life was found in most cases, with a significant decrease in clearance (46 +/- 17 L/hr on day 3 versus 28 +/- 10 L/hr on day 15). This resulted in a continuous increase in the CsA blood level. The terminal half-life varied considerably among the patients (24-93 hr) and did not correlate with other pharmacokinetic parameters. A good correlation (r = 0.9589) was observed between CsA trough levels before discontinuation of CsA and the increment in renal function two weeks after conversion to azathioprine. This indicates that short-term CsA treatment induces a dose-dependent reversible nephrotoxic effect in renal transplant recipients.