Abstract
Cimetidine, 400mg a day, was orally administered to the patients on chronic hemodialysis for a 4-week period and a 6-week period to determine mainly the reduction rates of serum parathyroid hormone (PTH).
1) Changes in PTH after the short-term cimetidine therapy.
In the group with markedly increased PTH (the pre-cimetidine therapy level of PTH being 8.03±3.63ng/ml), PTH dropped significantly to 5.67±2.94ng/ml within 4 weeks, but tended to increase after the cessation of cimetidine therapy. In the group with moderately increased PTH (the pre-cimetidine therapy level of PTH being 3.36±0.88ng/ml), PTH decreased moderately to 2.56±0.66ng/ml within 4 weeks. This decrement was not significant. In the both groups, serum calcium and phosphate did not show any significant change throughout the period of cimetidine therapy, suggesting that PTH reducing activity of cimetidine was not due the secondary effect of serum calcium.
2) Changes in PTH after the long-term cimetidine therapy.
The PTH levels in 5 patients belonging to the group with markedly increased PTH were 7.66±3.91ng/ml before the cimetidine therapy, but dropped significantly to 5.17±3.05ng/ml in one month and to 3.63±1.12ng/ml 6 months after the cimetidine treatment. In the patient with abnormally high PTH level (14.39ng/ml), even a minimal dose of 1-alpha-(OH)-D3 induced hypercalcemia promptly, thus a sufficient amount of 1-alpha-(OH)-D3 could not be given, and the patient complained of severe bone pain. However, as the PTH level decreased with cimetidine therapy, an increased dose of 1-alpha-(OH)-D3 did not produce hypercalcemia, and bone pain disappeared.
3) Changes in the serum cimetidine concentration and it's reduction rates during and after hemodialysis.
After the oral administration of cimetidine 200mg, the serum cimetidine concentration reached a maximal level of 1.84±0.63μg/ml in 4 hours and decreased gradually thereafter to 0.86±0.33μg/ml by 10 hours. Even after the continuous administration for 4 weeks, there were no signs of the accumulation.
The reduction rate of serum cimetidine concentration per single hemodialysis was 69.2±10.5% after 5 hours of hemodialysis using a dialyzer with a mean membrane surface area of 1.3M2.
Cimetidine therapy to the patients with uncontrollable secondary hyperparathyroidsm in considered worthwhile to attempt before performing subtotal prathyroidectomy.
