Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with end-stage renal disease commonly develop secondary hyperparathyroidism. Calcitriol may be administered to such patients to decrease the synthesis and secretion of parathyroid hormone (PTH) and to help maintain calcium and phosphorus homeostasis. However, the doses of calcitriol required to suppress serum PTH concentrations can lead to hypercalcemia or hyperphosphatemia in many patients undergoing hemodialysis. Paricalcitol is a new vitamin D analogue that is safe and effective in suppressing elevated concentrations of PTH in patients with established hyperparathyroidism who are maintained on chronic hemodialysis. As with vitamin D, the biologic action of paricalcitol is mediated through activation of the vitamin D receptor (VDR). The VDR functions as a ligand-induced transcription factor regulating the rate of expression of genes that are involved in controlling not only calcium homeostasis and bone remodeling but also hormone secretion, inhibition of cell growth, and induction of cell differentiation. In vitro studies have shown that paricalcitol inhibits PTH secretion from bovine parathyroid cells in a dose-dependent manner. Studies in renally insufficient rats demonstrated that paricalcitol caused approximately 10 times less elevation of serum calcium concentrations than calcitriol. In clinical studies, paricalcitol effectively decreased PTH by about 60% over a 12-week period. Mean serum concentrations of calcium were significantly increased but remained within the normal range. There were occasional (5/414 determinations) transient elevations in serum calcium above the upper limit of normal in some (5/401) patients. Serum phosphorus values did not change significantly compared with baseline, although they tended to be slightly higher in the paricalcitol-treated group than in the group receiving placebo. Elevations of the calcium-times-phosphorus product were relatively few but occurred more often in the paricalcitol than in the placebo group. The terminal half-life of paricalcitol was 5 to 7 hours in healthy subjects; in patients undergoing hemodialysis, it was 14 hours. Adverse events associated with paricalcitol use included, among others, chills, feeling unwell, fever, sepsis, palpitations, dry mouth, gastrointestinal bleeding, nausea, vomiting, edema, light-headedness, and pneumonia. Paricalcitol should be considered as an alternative to calcitriol in the treatment of patients who are undergoing maintenance hemodialysis for end-stage renal disease, as it has a decreased potential to induce hypercalcemia and hyperphosphatemia. Additional studies are required to determine the long-term effects of therapy.
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PMID:Paricalcitol, a new agent for the management of secondary hyperparathyroidism in patients undergoing chronic renal dialysis. 1032 13

Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580). In a rat model of CKD induced by 5/6 nephrectomy, oral administration of evocalcet efficiently suppressed the secretion of parathyroid hormone (PTH). With regard to the gastro-intestinal effects, cinacalcet induced a significant delay in gastric emptying in rats, while evocalcet did no marked effects on it. Evocalcet also demonstrated the less induction of emesis compared to cinacalcet in common marmosets. The pharmacological effects of evocalcet were observed at lower doses because of its higher bioavailability than cinacalcet, which may have contributed to the reduced GI tract symptoms. In addition, evocalcet showed no substantial direct inhibition of any CYP isozymes in in vitro liver microsome assay, suggesting a better profile in drug interactions than cinacalcet that inhibits cytochrome P450 (CYP) 2D6. These findings suggest that evocalcet can be a better alternative to cinacalcet, an oral calcimimetic agent, with a wider safety margin.
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PMID:A novel calcimimetic agent, evocalcet (MT-4580/KHK7580), suppresses the parathyroid cell function with little effect on the gastrointestinal tract or CYP isozymes in vivo and in vitro. 2961 98