vitamin-d-2 and Vomiting

Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations.. One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease.. The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste.. This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Calcium; Ergocalciferols; Female; Humans; Hyperparathyroidism, Secondary; Hypocalcemia; Kidney Failure, Chronic; Male; Middle Aged; Nausea; Parathyroid Hormone; Phosphorus; Taste Disorders; Time Factors; Vomiting

Large intramuscular doses of a water-miscible preparation of vitamin A (500,000 I.U. retinyl acetate/ml), vitamin E (50 I.U./ml) and vitamin D2 (50,000 I.U./ml) were administered to young monkeys (Macacus fascicularis) weighing 1-1.8 kg. At vitamin A doses equivalent to 200 mg retinol/kg or higher, early signs of acute toxicity included yawning, apparent drowsiness, nausea and vomiting, head shaking, neck hyperextension, motor hyperactivity and coordination. These immediate signs were first noted 3-35 minutes after injection. Following apparent recovery at 1-2 hrs, longer term signs of toxicity, such as decreased activity, malaise, drowsiness, loss of appetite, loss of weight, and itchiness of the skin, appeared within 1-6 days, depending on the dose. Monkeys receiving the highest lethal doses became progressively weaker, showed labored breathing, lapsed into a coma, lost simple reflexes and then died. Respiratory failure usually preceded the cessation of heart beat. In some monkeys on a lower but lethal dose, death was preceded by generalized convulsive seizures. The time of onset of the first sign and survival time were inversely proportional to the dosage, but in individual monkeys no correlation existed between onset time and survival time. Female monkeys seemed to succumb faster to a lethal dose than male monkeys. All animals receiving the equivalent of 300 mg retinol/kg died. Under the conditions used, the LD50 was estimated to be 168 mg retinol (560 000 I>U.) per body weight.

Topics: Animals; Body Weight; Ergocalciferols; Female; Humans; Lethal Dose 50; Macaca fascicularis; Male; Nausea; Sleep Stages; Stereotyped Behavior; Vitamin A; Vitamin E; Vomiting