Effect of renal impairment on the pharmacokinetics of memantine.

The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CL(CR)): normal renal function (> 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7). Mean memantine maximum plasma concentration (C(max)) was similar in the groups (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to C(max) (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine determined from mean area under the plasma concentration-time curve was 1.62-, 1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal impairment, respectively, as compared to controls with normal renal function. Mean memantine plasma elimination half-life increased according to increasing renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%, respectively). These results are the same as those in the previous study on caucasian individuals, when compared per body weight. It is suggested that the dose of memantine should be halved in patients with renal impairment.

[Case of fanconi syndrome positive for anti-M2 antibodies revealed by severe hypokalemia and multiple bone fracture].

A 38-year-old female developed pain in the right leg in 2006. In 2007, the diagnosis of femoral head necrosis was made based on MR images, and femoral head prosthetic replacement was performed. In April 2009, she visited a local hospital for low back pain, and was referred to our department due to electrolyte abnormalities on hemanalysis. Since marked hypokalemia (K=2.5 mEq/L), hypophosphatemia, hyperchloric metabolic acidosis, proteinuria, and urinary blood sugar suggested Fanconi syndrome, she was admitted for close examination. Bone survey showed a marked decrease in the amount of bone particularly in the four limbs and fracture at the proximal 1/3 of the left ulnar bone. In the lumbar spine, scoliosis and vertebral deformity were observed. Since impaired P re-absorption and unselected aminoaciduria and osteomalacia were also present, the diagnosis of Fanconi syndrome was made. On admission, ventricular tachycardia developed due to hypokalemia, requiring immediate electrolyte correction. For differentiation from acquired Fanconi syndrome, various examinations were performed. No apparent cause was found except for the positive antimitochondrial antibody-M2 (anti-M2). In this case, no data suggested liver dysfunction, and subsequent liver biopsy also showed no significant pathological findings pointing to PBC. We encountered a patient with Fanconi syndrome positive for anti-M2. This case may attract interest, particularly in the mechanism of nephropathy due to anti-M2, and therefore, this case is reported with a literature review.