The patient was a 67-year-old man with chronic glomerulonephritis. He received a heminephrectomy due to renal tuberculosis in 1955. His renal function progressively deteriorated, and albuminuria and hematuria had been present since his 30s. He first visited our hospital in 1999, and over the years his blood urea nitrogen and serum Cr levels gradually increased. In 2008, his estimated glomerular filtration rate and 24-hour Cr clearance reached 7.1 ml/min/1.73 m2 (CKD stage 5) and 11.2-15.4 ml/min, respectively. He was hospitalized for the preparation for hemodialysis.
The patient began to complain about forgetfulness and stumbling about 4 months before hospitalization. Plain cranial MRI showed prominent hippocampal and cerebrocortical atrophy, and he was diagnosed with AD. Administration of DPZ was started at a low dose of 1.5 mg/day in consideration of his deteriorated renal function. As the serum Cr level was elevated after 2 weeks of treatment, the dose was changed to 3 mg twice a week, and then finally to 5 mg twice a week. His renal function has been stable since then.
Figure 3 shows changes in the renal function, MMSE, and HDR-S over time. Overall, MMSE and HDR-S scores remained almost unchanged 7 months after DPZ administration.
The plasma concentration was measured at 0, 1, 2, 3, 4, 6, 9, 12, 24, 48, and 72 h after the administration of 5 mg of DPZ following about 4 months of treatment with DPZ (fig. 4). The trough level (9.1 ng/ml) with this dose was the same as or slightly lower than the trough level in healthy male adults with the 5-mg daily dose (10-15 ng/ml). The change in the plasma concentration in the initial 24 h was similar to that in healthy male adults with 5 mg/day. However, since this patient received DPZ twice a week, it was not reasonable to compare the Cmax in this patient with the Cmax in the DI according to which volunteers received daily administration. The AUC for 7 days was 3,681.09 ng h/ml in healthy male adults with the 5-mg daily dose, while the AUC was 2,096.3 ng h/ml in this patient with the 5-mg dose twice a week. As the plasma concentration in this patient had only two peaks a week, the AUC per week was expected to be lower than that under daily administration. The tmax was 1-2 h for this patient, which was almost the same as the tmax in healthy male adults with single-dose administration (table 1). No side effects were observed in this patient throughout the observed period.