Related Experiment Videos
The effect of renal function on the pharmacokinetics of gemfibrozil
J R Evans1, S C Forland, R E Cutler
1Department of Medicine, Loma Linda University Medical Center, Jerry L. Pettis Memorial Veterans Hospital, CA 92357.
Study Objective:
to determine the effect of renal function on the pharmacokinetics of gemfibrozil following single and multiple oral doses.
Design:
nonrandomized; paired studies of single versus multiple doses.
Setting:
patients enrolled in a veterans hospital renal subspecialty clinic.
Patients:
17 male patients 57 to 74 years old selected for various levels of renal function, including end-stage renal disease.
Interventions:
patients initially received 600 mg of oral-gemfibrozil followed by sequential venous blood sampling. Seven to 14 days later, the patients started receiving gemfibrozil, 600 mg bid. Venous blood samples were obtained over the following 10 days and frequently during a 24-hour washout phase.
Measurements And Main Results:
peak gemfibrozil concentrations (mg/L) were 11.1 (3.9 SD) for the single dose and 10.2 (3.8) for the multiple-dose study. Time to peak concentration (hr) was 2.1 (1.0) and 1.8 (0.6), respectively. The mean half-life of elimination (hr) from the single-dose study was 6.4 (11.8) compared with the multidose study of 3.0 (3.1), which did not reach statistical significance (P = .25). The difference between the area under the curve for the single versus the multiple-dose study approached statistical significance (P = .054). The coefficient of determination for creatinine renal clearance versus the plasma clearance of oral gemfibrozil was 0.009 (P = .72) for the single-dose regimen and 0.331 (P = .016) for the multiple-dose study.
Conclusion:
the half-life of gemfibrozil is independent of renal function for both single- and multiple-dose regimens. Dosing schedules do not require alteration for renal insufficiency.