Abstract
HIH is a serious complication in patients with maintenance HD therapy. We reported that DOPS, a synthetic precursor amino acid of norepinephrine (NE), was effective not only for HIH during HD but also for orthostatic hypotension and fatigue after HD. DOPS and it s metabolites were known to be excreted in urine. So, in this study, we evaluate the pharmacokinetics of oral dose of DOPS in the ex erimental rat with renal failure and in the patients with maintenance HD. As results from the study in the rats with 14C-DOPS, POPS metabolism was shown to be essentially unchanged in uremia, and DOPS did not accumulate in uremic rat. In patients suffering HIH with three times/week regular HD (4hrs), 300mg of DOPS was administered orally 1hr before the initiation of HD. Plasma DOPS concentration gradually increased during till, and reached a peak after 6hrs (1hr after HD) of the dose. It disappeared 24 hrs later. Plasma NE levels with DOPS were significantly higher than those without DOPS during 24 hrs, and highest (1.05±0.22ng/ml) after 6 hrs of the administration of POPS. The high level of NE was speculated to be contribute for the improvement of HIH and some complaints during and after HD. In long-term treatment with DOPS, plasma DOPS were not detected before the next administration periods, and plasma NE levels did not reachd to the unphysiological concentration in any patients. In conclusion, the safety and the efficacy of oral DOPS therapy for HIH were also supported by this pharmacokinetic study.
