Equivalent pharmacokinetics of mycophenolate mofetil in African-American and Caucasian male and female stable renal allograft recipients.

African-American (AA) renal transplant recipients require higher doses of mycophenolate mofetil (MMF) than Caucasians. A hypothesized pharmacokinetic (PK) difference was tested in stable renal transplant recipients. Whole blood was collected before, and 20, 40 and 75 min, and 2, 3, 4, 6, 8 and 12 h after the MMF dose. Mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were analyzed using HPLC. Analysis of variance was performed for the primary end-points of dose-adjusted PK parameters AUC0-12 and Cmax of MPA using log-transformed values. Differences between races and genders were estimated: 90% confidence intervals (CI) were calculated. Back-transformation gave estimates of the race and gender ratio and their CI. Equivalence of the groups was determined if the 90% confidence limits were included in the interval (0.80, 1.25). The calculated PK parameters were comparable among the four subgroups (Caucasian, AA, Male, Female). The 90% CIs for the ratio of dose-adjusted AUC0-12 of MPA between races were between 89.7 and 112.9%. There were no race, gender or race-by-gender effects (p-values = 0.196) nor differences between diabetics and nondiabetics. This study demonstrates that dosing requirement for MMF in AA and Caucasians is unlikely to be related to different exposures to MPA.

Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment.

The pharmacokinetics of the low-molecular-weight heparin enoxaparin were evaluated in 12 healthy volunteers and 36 patients with mild, moderate or severe renal impairment. Enoxaparin was administered once daily by subcutaneous injections at a dose of 40 mg for 4 days and venous blood samples were taken over a 5-day period to determine antifactor Xa and antifactor IIa activity and the activated partial thromboplastin time. Adverse events were also recorded. The results for anti-Xa activity showed that the rate of absorption of enoxaparin was similar across the four groups of study participants. The elimination half-life increased with the degree of renal impairment, and this relationship was more evident after repeated dosing. Anti-Xa exposure was not significantly different between healthy volunteers and patients with mild or moderate renal impairment, but was significantly increased in patients with severe renal impairment (creatinine clearance < or =30 ml/min). Anti-Xa clearance decreased with the degree of renal impairment after repeated dosing, but only the difference between patients with severe renal impairment and healthy volunteers was statistically significant, the clearance on Day 4 being 39% lower in patients with severe renal impairment than in healthy volunteers (P=.0001). Anti-IIa activity was low in all study participants, and the activated partial thromboplastin time was not significantly different between the study groups. In conclusion, the clearance of enoxaparin is reduced in patients with severe renal impairment. Dose adjustment of enoxaparin may need to be recommended in these patients, but no recommendation can be made in patients with mild or moderate renal impairment.