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| |  Pharmacokinetics Of Prandin Similar In Young And Elderly Adults PRINCETON, NJ -- April 13, 1999 -- Novo Nordisk Pharmaceuticals, Inc.’s oral antidiabetic drug (OAD) Prandin(TM) (repaglinide) tablets, is tolerated in the elderly as well as in young adults, a new study shows. The drug's short half-life and mode of excretion from the body may help to lower the risk of hypoglycemia in elderly patients with type II diabetes, many of whom have declining kidney function. The study, accepted for publication in this month’s issue of Clinical Therapeutics, reports that the drug's pharmacokinetics -- the action of the drug in the body over a period of time -- are similar in both young and elderly subjects, meaning that age does not significantly influence how Prandin is handled by the body. The open-label comparative study evaluated a range of pharmacokinetic parameters (including time to maximal concentration and half-life) in 24 healthy adults, half of whom were elderly (65 or older). Generally, a patient's age has the potential to complicate drug treatment decisions because renal function declines naturally over time, making it more difficult for the kidneys to eliminate antidiabetic drugs from the body. This decline in function places elderly patients at an increased risk for hypoglycemia (low blood glucose), according to the study's investigators. The most frequently prescribed OADs, sulfonylureas (SUs), are metabolised by the liver and excreted primarily by the kidneys. As a result, elderly patients treated with long-acting SUs and SUs with active metabolites that remain in the bloodstream are particularly susceptible to hypoglycemia, especially if they miss meals or if their hepatic, renal, or cardiovascular function is impaired. The study concluded the pharmacokinetics of Prandin may make it an appropriate treatment for some elderly patients with type II diabetes who also have declining renal function. Unlike SUs, Prandin, the first in a new class of drugs called meglitinides, is metabolised in the liver and eliminated primarily in the bile. In addition, none of its metabolites contributes to its blood-glucose-lowering activity. Since Prandin is not dependent upon renal excretion, it may lower the risk of hypoglycemia in elderly patients. Of the estimated 16 million Americans with diabetes, approximately 6.3 million are over the age of 65. To reduce the risk of moderate-to-severe hypoglycemia in elderly patients, the American Diabetes Association (ADA) and the European Type II Policy Group recommend use of short-acting drugs. However, most commonly prescribed OADs, like SUs, are long acting. Prandin meets the need for a short-acting oral medication. It is rapidly absorbed, reaches maximal concentration in approximately one hour and has a biologic half-life of approximately one hour. The short half-life and meal-related dosing of Prandin enable it to augment the body's natural response to food intake, increasing insulin release after each meal when blood glucose levels are high. Between meals and during the night, insulin levels return toward baseline, which can reduce the occurrence of severe hypoglycemia and hyperinsulinemia (excess insulin). In addition, Prandin can be used cautiously in patients with renal impairment or renal failure requiring hemodialysis and in patients with impaired liver function. Hypoglycemia is a condition in which glucose in the blood is abnormally low, resulting in symptoms such as unusual hunger, feelings of anxiousness, shaking, rapid heart rate, impaired vision, headache, irritability, sweating, weakness or fatigue. If left untreated, hypoglycemia can result in coma, a life-threatening condition or death. A total of 24 healthy volunteers (without diabetes) were enrolled into two groups, with an equal number of men and women. One group consisted of 12 young adult subjects (between 18 and 40 years of age; mean age 33 years) and the other of elderly subjects (age 65 or over; mean age 67 years). The pharmacokinetic parameters under assessment were: area under the curve (AUC), maximal concentration (Cmax), time to maximal concentration (Tmax) and half-life (T1/2). All were derived from serum PRANDIN concentrations after single-dose and multiple-dose regimens. After a single dose, mean AUC and Cmax values for both groups were found to be not significantly different. Tmax in elderly subjects (0.7 hr) was comparable to young adult subjects (0.8 hr). After multiple dosing, the AUC, Cmax and Tmax values of serum Prandin were also similar in both groups. Comparable T1/2 values were obtained for elderly (0.9 hr) and young adult subjects (1.0 hr). Prandin was well tolerated and adverse events throughout the course of study consisted of hypoglycemia and symptoms associated with hypoglycemia. For the purposes of this study, hypoglycemic events were confirmed by a blood glucose meter reading below 45 mg/dl. Five out of seven young adults and five of 10 elderly subjects reported events such as sweating, hunger, dizziness, tremor, nausea, headache and fatigue. The healthy subjects in this study were not being infused with intravenous glucose to counter-balance the glucose-lowering effect of Prandin. Therefore, the occurrence of hypoglycemia and associated symptoms observed in the study was not unexpected, since the intended therapeutic effect of Prandin is to lower blood glucose. All 24 enrolled subjects completed the study and data for all subjects were included in the analyses. Prandin has been approved by the United States Food and Drug Administration for first-line therapy as an adjunct to diet and exercise to lower the blood glucose in patients with type II diabetes. Prandin is also indicated for use in combination with metformin in patients inadequately controlled by either drug alone. In long-term clinical trials with Prandin versus sulfonylureas, no participants on Prandin reported hypoglycemia that resulted in coma or required hospitalisation. In these clinical trials, hypoglycemia was reported in 16 percent of Prandin-treated patients and 20 percent of sulfonylurea-treated patients (glyburide and glipizide). The most common adverse events leading to discontinuation in these trials were hyperglycemia, hypoglycemia and related symptoms. Other than hypoglycemia, the most common side effects reported in clinical trials were cold- and flu-like symptoms, headache, diarrhea, joint ache and back pain.
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