"No period" pill, three other drugs get green light from FDA
The United States Food and Drug Administration (FDA) recently approved four new drugs-a "no period" contra-ceptive, a transdermal patch for early Parkinson's disease, an antiviral to prevent recurrence of hepatitis B, and an anti-bacterial ointment for skin infections.
Lybrel, a new birth-control pill that eliminates a woman's monthly periods, provides a steady low dose of hormones over 28 days, unlike traditional oral contraceptives that deliver pregnancy-preventing hormones with a 21-days-on and seven-days-off cycle. The continuous delivery of the hormones prevents the stimulation of a menstrual cycle. This is the first time that federal regulators have signed off on the practice of eliminating the pill-free or placebo interval, which stimulates a menstrual cycle. "For those women seeking contraceptive options and who are interested in putting their period on hold ... Lybrel may be an appropriate choice," said Ginger Constantine, vice president for women's health care at Wyeth Pharmaceuticals, which developed Lybrel. The FDA warned that 41 percent of women using Lybrel in a clinical study experienced unscheduled bleeding, although these occurrences declined over time. "Health-care professionals and patients are advised that when considering the use of Lybrel, the convenience of having no scheduled menstruation should be weighed against the inconvenience of unscheduled bleeding or spotting," the FDA said. The elimination of a regular period could also make it difficult for women to recognize if they have become pregnant, it warned. But some critics say the elimination of a period as a "lifestyle choice" could be bad for women's health. "Menstrual suppression is unnatural," health psychologist Paula Derry wrote in an editorial in the British Medical Journal. "A drug [that] chronically overrides the physiological changes associated with the menstrual cycle [is] creating a hormonal environment that is not found in nature," she wrote. Wyeth said 97 percent of gynecologists "thought it is safe to use oral contraceptives continuously, without a placebo phase, in the appropriate patient population," according to a Gallup survey of 205 obstetrician-gynecologists and 200 nurse practitioners. Lybel is expected to generate US$40 million in sales in 2007 and US$235 million a year through 2010. It will be available in the US in July.
Neupro (rotigotine transdermal system), manufactured by Schwarz Bioscience, is the first skin patch approved to treat symptoms of early Parkinson's disease. Rotigotine, a dopamine agonist, is delivered continuously through the skin using a silicone-based patch that is replaced every 24 hours. It works by activating dopamine receptors in the body, mimicking the effect of the neurotransmitter dopamine. The effectiveness of Neupro was demonstrated in one fixed-dose-response study and two flexible-dose studies. The parallel group studies were randomized, double-blinded, and placebo-controlled, and involved 1,154 patients with early Parkinson's who were not taking other Parkinson's medications. The most common side effects included skin reactions at the patch site, dizziness, nausea, vomiting, drowsiness, and insomnia, most of which are typical of this class of drugs.
HepaGam B prevents hepatitis-B reinfection in certain liver-transplant patients. Dr. Jesse Goodman, director of the FDA Center for Biologics Evaluation and Research, said the approval provides a new treatment option for the reduction of hepatitis-B recurrence in liver-transplant patients with a prior history of the disease. "It is the first immune globulin product-one of several classes of proteins derived from human plasma-approved for this use." HepaGam B works by providing an immediate immune response to the virus. It is manufactured by Cangene Corp. of Winnipeg, Canada from human plasma collected at US-licensed plasma centers from healthy donors.
Altabax (retapamulin ointment) is a topical treatment for impetigo, a skin infection caused by bacteria. It is indicated for use in patients nine months or older. Retapamulin is a new molecular entity not previously approved in the United States. Altabax was approved on the basis of effectiveness data from a placebo-controlled study supported by a study comparing Altabax with another antibiotic. The safety database contained approximately 2,000 Altabax-treated adults and children nine months and older, and about 1,000 similar patients who received different antibiotics or placebo. The most common Altabax-related adverse event was irritation at the site of the application. Altabax is manufactured by GlaxoSmithKline. M
LONDON Cervarix, GlaxoSmithKline's (GSK) cervical-cancer vaccine, has been granted a license by the Therapeutic Goods Administration (TGA) of Australia for the prevention of cervical cancer and precancerous lesions associated with the most common cancer-causing human papillomavirus (HPV) types. The vaccine is now approved in Australia, the first country to do so, for use in females 10 to 45 years old. Jean Stephenne, president of GSK Biologicals, said the approval is a key milestone toward eradicating the burden of cervical cancer for all women, especially as this is the first cervical-cancer vaccine that is explicitly indicated anywhere in the world for women over the age of 26. "This vaccine heralds a major scientific breakthrough in cervical-cancer prevention and demonstrates GSK's commitment to developing innovative vaccines. It is great news for us and this vaccine will be a key driver in GSK's future growth," she said. Cervarix has consistently shown high levels of efficacy in preventing precancerous lesions due to cancer-causing HPV types 16 and 18 inclinical trials involving over 40,000 females. Data also showed preliminary evidence of additional protection against infection with cancer-causing virus types other than virus types 16 and 18. These trials showed Cervarix has a good safety profile and is generally well tolerated. Cervarix is formulated with a novel proprietary adjuvant system called AS04 which is designed to enhance immune response and increase the duration of protection. Published data have shown that this adjuvant formulation provides a stronger and longer-lasting immune response compared with the same vaccine composition formulated with conventional aluminum hydroxide adjuvant alone. "We are especially excited about Cervarix, the first cervical-cancer vaccine to feature one of our novel adjuvant systems. Our goal is to provide the best possible protection for women against cervical cancer," Stephenne said. GSK is also seeking apporval for Cervarix in the United States, Europe, and several countries in Africa, Asia, and Latin America. Cervical cancer, the second leading cause of cancer in women under 45, claims over 270,000 lives worldwide every year. It occurs when HPV infection becomes persistent and progresses to cancer. Up to 50 to 80 percent of women will acquire an infection in their lifetime, with the risk of persistence increasing with age. This is why experts recommend that women over 26 also be protected against cancer-causing HPV types to reduce the risk of infection becoming persistent and progressing to cervical cancer. In humans, approximately 100 types of HPV have been identified to date. Of these, 15 are considered to cause cervical cancer. Virus types 16 and 18 are responsible for approximately 70 percent of cervical cancers globally. M
NEW YORK The United States Food and Drug Administration (FDA) has approved atorvastatin calcium (Lipitor) as treatment to reduce the risk of nonfatal heart attacks, fatal and nonfatal strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is the first cholesterol-lowering medication to receive FDA approval for the reduction of the risk of hospitalization for heart failure. Pfizer said this new approval expands the use of Lipitor to patients at high risk for cardiovascular events because of established heart disease such as prior heart attack, prior heart surgery, or chest pain with evidence of clogged arteries. Previously, Lipitor was approved to reduce cardiovascular events in patients without heart disease. "These new indications are important since many patients who have heart disease remain at risk for another cardiovascular event, and now these indications broaden the means to reduce their risk," said Dr. John LaRosa, president and professor of medicine at the State University of New York Downstate Medical Center in Brooklyn and lead investigator for the Treating to New Targets (TNT) trial. "The significant reduction in cardiovascular events seen in the TNT trial can now be applied to everyday practice and benefit people with heart disease in the United States." The approval was based on results from the TNT trial and supported by findings from the Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL) trial. The five-year TNT study involved 10,000 patients with both heart disease and elevated levels of low-density lipoproteins (LDL). It is the longest and largest study on the efficacy and safety of Lipitor 80 mg. In this study, patients taking Lipitor 80 mg had a significant 22-percent reduction in the risk of major cardiovascular events over and above patients taking Lipitor 10 mg. In addition, patients treated with Lipitor 80 mg had a significant 26-percent reduction in the risk of hospitalization for heart failure. There were more serious adverse events and discontinuations due to adverse events with Lipitor 80 mg compared with Lipitor 10 mg. However, there was no difference in the overall frequency of treatment-related adverse events. "Lipitor is the world's most extensively studied cholesterol-lowering medication, and is supported by a large clinical-trial program that includes more than 10 cardiovascular outcomes trials with over 50,000 patients across a broad spectrum of risk," said Dr. Michael Berelowitz, Pfizer senior vice president of global medical. "Lipitor is the only statin that offers a unique combination of proven significant cardiovascular-event reductions, impressive average LDL lowering of 39 percent to 60 percent, and a well-established safety profile." M BusinessWire
PARIS A drug tested on lab mice slows and may even halt the progress of Parkinson's disease, offering the brightest pharmacological hope in decades of rolling back this tragic disease. Isradipine (DynaCirc), already licensed for hypertension, rejuvenated ageing dopamine cells, researchers said. The outcome among mice was so promising that the team now plans on conducting trials on human volunteers. "Our hope is that this drug will protect dopamine neurons, so that if you began taking it early enough, you won't get Parkinson's disease, even if you were at risk," said lead researcher James Surmeier, professor of physiology at Northwestern University in Chicago. "It would be like taking a baby aspirin every day to protect your heart." Parkinson's is an incurable, degenerative disease of the central nervous system that causes uncontrollable shaking, along with impaired speech and movement. The cause is a loss of dopamine, a chemical messenger that helps direct movement. The substance is provided in a part of the brain called the substantia nigra. Most pacemaking neurons use sodium ions to produce a regular electrical signal. But the new research unexpectedly found that dopamine cells, when they reached adulthood, start to depend more and more on calcium ions. This discovery is important, because calcium ions are far more troublesome to control than their placid sodium counterparts: the cell uses up lots of energy, either to round up and sequester the calcium or pump it out. As a result, the dopamine cells become stressed on reaching their calcium-addicted adulthood and die prematurely. Surmeier's hunch was to try isradipine, which blocks the channels in the cell surface that admit calcium. Tested on lab-dish cells and then on mice that had been genetically engineered to have Parkinson's, Surmeier's team found that within a few hours of being exposed to the drug, the neurons reverted to their youth-like state, of using sodium. This lowered the cells' stress level, making them less vulnerable to the toxins, still poorly understood, that kills them. The study is published by Nature. So far the work has only been carried out on animals, and more needs to be done to assess the drug's effect on humans. But Surmeier voiced cautious hopes it could be the first treatment to prevent or slow the progression of this devastating disease. The mainstay treatment for Parkinson's is L-DOPA, a drug that the brain converts into dopamine. At first, L-DOPA has a seemingly miraculous effective on symptoms. The problem, though, is that it becomes less and less effective as time wears on and the disease progresses, forcing doctors to raise the dose, which induces unwanted side effects, including spastic, jerky movements. So, if isradipine can slow the death of dopamine neurons, the L-DOPA "honeymoon" could be significantly extended. "If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance," said Surmeier. M AFP
Rituximab (MabThera), the first in a number of novel in Roche's emerging autoimmune portfolio, is now available in the Philippines for treatment of rheumatoid arthritis (RA). Roche launched the drug in a symposium dubbed Redefining the Art of Rheumatoid Arthritis Treatment attended by officers and members of the Philippine Rheumatology Association (PRA) at the Ayala Museum in April. Saying alternate biologic therapies are needed for RA, Dr. Peter Thomas Nash, senior lecturer at the University of Queensland and chair of the therapeutics committee of the Australian Rheumatology Association, presented clinical trials showing that rituximab halts damage to joints and provides lasting treatment success. Clinical trials with rituximab, the first and only selective B-cell therapy for RA, showed that RA patients given the drug achieved improvement in general quality of life, said Nash. In these trials, 72 percent of patients who received a first course of treatment and 69 percent of those who received a second course experienced a clinically meaningful change in their physical function based on the Health Assessment Questionnaire Disability Index. They also experienced improvement in both mental and physical components of their quality of life as measured by the Short Form Health Surveys. According to Dr. Clemente Amante, chair of the PRA's rheumatoid-arthritis special interest group, RA is one of the most common inflammatory arthritis among Filipino patients. "Our experience has shown that it is a progressive disease that leads to functional disability and poor quality of life as well as increased mortality," he said. "The recent discovery of the role of B cells in the progression of RA has led to the emergence of a unique RA therapy seen to provide physicians with a new form of therapy that may lead to improved and better clinical outcome among patients." Commented Dr. Caroline Arroyo, PRA vice president: "When we speak of suffering, rheumatoid arthritis is perhaps one of the most debilitating diseases of the modern world. What we have in our hands is a breakthrough product that can arrest the progression of RA, consistently relieve patients from excruciating pain, and enable them to return to normal life." For his part, Dr. Rolf Ammelburg, Roche general manager, said MabThera "is set to make a substantial difference to people suffering from RA ... and bring relief to patients who have a need for more than the traditional therapies." M
BASEL, Switzerland Appropriate management of renal anemia with epoetin beta (Recormon) increases the number of patients in patients with chronic kidney disease (CKD) on dialysis who gain control of hemoglobin levels in line with expert guidelines. Final results from the 13-nation "Gain effectiveness in anemia treatment with Recormon" (GAIN) study in 4,264 patients showed that the proportion of patients attaining the hemoglobin target of 11 g/dL or greater increased from 48.3 percent at baseline on other erythropoiesis-stimulating agents (ESAs) to 55.5 percent on Recormon at seven to 12 months and 59 percent by the end of the study (13 to18 months). The results were presented at the World Congress of Nephrology in Rio de Janeiro, Brazil, in April. The GAIN study was designed to assess the effectiveness and safety of Recormon in reaching and maintaining hemoglobin levels in unselected patients on hemodialysis in Europe. Current treatment guidelines in the European Union advise that patients with CKD should maintain a target Hb of 11 g/dL or greater. The number of patients administered Recormon who maintained hemoglobin levels of 10 to 12 g/dL increased during the six-month observational phase from 57 to 62 percent. This was maintained during the 12-month follow-up period, with 61 percent of patients in this range by the end of the study. For patients receiving once-weekly Recormon, 69 percent remained in this range during the 12-month follow-up and 66 percent by the end of the study. These results are important as current guidelines suggest that hemoglobin levels outside this range could result in harmful effects on the kidney, heart, and cardiovascular system. No patients were found to have antierythropoietin antibodies while receiving Recormon during the 18-month study. "The GAIN study confirms that once-weekly use of subcutaneous epoetin beta not only improves anemia management for dialysis patients, but could also result in important cost savings in the clinic. This is very good news since renal anemia requires long-term treatment," said Dr. T. Weinreich, Nephrology Centre, Villingen-Schwenningen, Germany, who presented the results. GAIN was an uncontrolled, 18-month-long observational study set up to assess the real-world management of renal anemia in patients on hemodialysis throughout 13 countries in Europe. Following a three-month retrospective phase, in which patients received any ESA, patients entered a six-month observational phase in which they received Recormon either intravenously or subcutaneously. They continued a 12-month follow-up phase, in which they received Recormon, preferably by the subcutaneous route. Recormon was administered at dosing intervals of once weekly or more frequently. M
WASHINGTON Older vaccines used worldwide against tuberculosis could be more effective than the latest versions, according to a new study published in the Proceedings of the National Academy of Sciences. Researchers at the Pasteur Institute in Paris found multiple genetic mutations in strains of bacillus Calmette-Guerin (BCG), accidentally introduced as the microbe was cultured over decades, reduced the efficacy of the vaccine. They concluded that old and new vaccines should be retested in clinical trials to determine which are the most effective. "Early BCG vaccines may confer better protection against tuberculosis, a possibility that would benefit from formal evaluation in clinical trials," researchers said. BCG is a crippled derivative of Mycobacterium bovis, the microbe that causes tuberculosis in cattle, and is particularly effective in preventing tuberculosis in children, but results are variable in adults. Researchers looked at the entire genetic sequence of several BCG strains and found changes over time. By studying immune responses in infants, one vaccine strain called BCG Japan, an early strain developed prior to 1925, triggered a more powerful immune reaction than the vaccine strains BCG Danish, BCG Glaxo, and BCG Pasteur, which represented 66 percent of the vaccine doses administered in 1996. M AFP
WASHINGTON The Food and Drug Administration (FDA) approved the targeted anticancer treatment lapatinib (Tykerb) for use together with capectabine (Xeloda) for women with advanced metastatic breast cancer that is HER2 positive, saying tests showed the combination slowed the advance of the cancer. "[The] approval is a step forward in making new treatments available for patients who have progression of their breast cancer after treatment with some of the most effective breast-cancer therapies available," said Dr. Steven Galson, director of the Center for Drug Evaluation and Research. "New targeted therapies such as Tykerb are helping expand options for patients." The approval came after a clinical trial on 400 women suffering from advanced HER2-positive breast cancer. The FDA said the study showed a "statistically significant improvement" in the time to tumor progression in the group taking the combination of the two drugs. But they offered no data on survivors after the treatment, saying it was too early to make any determinations. Side effects associated with Tykerb, made by GlaxoSmithKline, include diarrhea, nausea, vomiting, and rash; and numbness, tingling, redness, and swelling in the hands and feet. Some 180,000 new cases of breast cancer are diagnosed each year. Annually 8,000 to 10,000 women die from metastatic HER2 breast cancer. M AFP
RESEARCH TRIANGLE PARK, North Carolina Adding the once daily, investigational medication ropinirole HCl (Requip XL 24-hour) extended-release tablets to existing levodopa (L-dopa) therapy for Parkinson's patients significantly reduced "off" time, allowing patients to continue their daily activities for a longer period of time. "Off time" describes the return of Parkinson's symptoms as a patient's medication wears off. Results of the Ropinirole 24-Hour Prolonged Release Randomized Controlled Study in Advanced Parkinson's Disease (EASE-PD adjunct study) published in the April 3 issue of Neurology show that adjunct treatment with Requip XL 24-Hour reduced "off time" by an average of more than two hours per day compared with pretreatment baseline. "Off time is a common phenomenon for Parkinson's patients. When symptoms like slowness of movement, tremor, and rigidity return due to wearing off of the patient's medication, it can be problematic, causing difficulty with simple activities and movement," said Dr. Rajesh Pahwa, director of Parkinson's Disease and Movement Disorder Center at the University of Kansas Medical Center and lead investigator. "These study results are significant, and show that with the investigational Requip XL 24-Hour added to L-dopa, patients can have more than two additional hours per day on average without experiencing the disabling symptom of off time." The study also included a wide variety of motor and nonmotor secondary end points, including "on time," which refers to the time during which medication is working and providing benefit, and "on time without troublesome dyskinesia," which refers to "on time" without involuntary movements interfering with function or causing discomfort. Requip XL 24-Hour significantly increased both parameters by 1.6 hours per day and reduced the percentage of "off time" by more than 12 percent compared to baseline. Requip XL 24-Hour also improved sleep problems associated with Parkinson. The treatment was generally well tolerated. The withdrawal rate due to adverse events was low (five percent) and similar for both Requip XL 24-Hour and placebo. The most common adverse events reported in patients taking Requip XL 24-Hour versus placebo were dyskinesia (13 v. three percent), nausea (11 v. four percent), dizziness (eight v. three percent), somnolence (seven v. four percent), hallucinations (six v. one percent), and orthostatic hypotension (five v. two percent). Requip XL 24-Hour is designed to be given once daily and to have a simpler and faster titration schedule. GlaxoSmithKline sponsored the study as part of the clinical development program for the investigational 24-hour extended-release formulation of Requip, which uses SkyePharma Plc's proprietary GeoMatrix technology. M
Merck Sharp and Dohme (MSD) Philippines recently launched sitagliptin (Januvia), a new drug for type 2 diabetes classified as dipeptidyl peptidase-4 (DPP-4) inhibitor. It is the first of its kind to be launched in Asia, where diabetes is nearing epidemic proportions. It is projected that in 2025, there will be 333 million diabetics worldwide. "The sad part is, most of the burden of this increase will come from our part of the world," said Dr. Araceli Panelo, executive director of the Institute for the Study of Diabetes Foundation. It is estimated that developing countries will account for 75 percent of diabetics in 2025. In welcoming the new addition to the antidiabetes armamentarium, Panelo noted that even with all the current therapeutic options, "very few patients can reach treatment goals." DPP-4 inhibitors work by affecting incretin hormones, enhancing the body's natural ability to control blood-sugar levels. The body has two major incretins both secreted by the intestines. Glucose-dependent insulinotropic polypeptide (GIP) and glucagons-like peptide 1 (GLP-1) work two ways to keep blood sugar at normal levels. First, they activate the release of insulin from the beta cells in the pancreas, allowing the body to absorb blood glucose. Second, they inhibit the release of glucagons from the pancreas' alpha cells, regulating the amount of glucose that the liver releases. In normal individuals, GIP and GLP-1 are responsible for 60 to 70 percent of the total postprandial insulin response, also known as the incretin effect. Incretins have a markedly decreased effect in diabetics compared with healthy individuals, leading to both delayed and reduced insulin release after glucose administration. DPP-4 is the enzyme responsible for degrading incretins. By inhibiting the DPP-4 enzyme, incretins remain in the body at higher concentrations and for longer periods, thereby enhancing their glucose-regulating effects. Clinical studies have shown that DPP-4 inhibitors are generally not associated with hypoglycemia, weight gain, gastrointestinal discomfort, or edema. While some diabetic drugs are notorious for their hypoglycemic side effects, this was observed less often among DPP-4 inhibitors because they are glucose-dependent. Said Dr. Elizabeth Paz Pacheco, past president of the Philippine Society of Endocrinology and Metabolism: "It's a very nice mechanism because whenever you're eating, you get the effect. When you're not eating, you don't get the effect. So it really helps us mimic our normal physiology closer than any other type of agent." Because of their unique mechanism of action, DPP-4 inhibitors complement other diabetes drugs and may be used either in combination with other drugs or as initial monotherapy. M C. Paraz, MD
A recent study has raised questions on the efficacy and safety of several biosimilar versions of epoetin alfa, a biopharmaceutical for the treatment of anemia. A biopharmaceutical is a medicine developed through biotechnology (genetic engineering). A biosimilar is a similar biological medicine approved for marketing after the patent of the innovator biopharmaceutical has lapsed. Epoetin alfa (EPO), a genetically engineered version of the natural hormone erythropoietin, stimulates the bone marrow to produce red blood cells. Doctors prescribe EPO to patients with anemia caused by chronic kidney disease, HIV medication, and cancer chemotherapy, as well as to decrease blood transfusions in surgery patients. "Several of the biosimilar epoetins we tested were inconsistent in quality and potency. They were not similar to the innovator epoetin alfa," said nephrologist Ajay Singh, associate professor of medicine at Harvard Medical School, who headed the study. Singh presented results of the study during a medical symposium on anemia management in chronic kidney disease organized in March by Janssen Pharmaceutica, a division of Johnson & Johnson (Philippines) Inc. Singh and his team tested 31 biosimilar epoetin samples from pharmacies in Brazil, Colombia, India, Indonesia, Iran, Jordan, Korea, Lebanon, Thailand, Venezuela, Vietnam, Yemen, and the Philippines against the European quality specifications for EPO. They found that 26 (84 percent) did not conform to European specifications while 22 (71 percent) contained additional forms of epoetin (basic isoforms), which can reduce efficacy. Two samples were contaminated with bacterial endotoxin, which poses serious risks to patient safety, and 17 contained significant amounts of aggregates, which can increase the risk of drug-related immunologic reactions. No biosimilar versions of EPO are currently marketed in Europe and the United States. Biosimilar epoetins are widely used in developing countries because they are cheaper than the innovator EPO. Singh noted that despite limited safety and efficacy data, biosimilar epoetins are prescribed under the assumption that they are as safe and effective as the original epoetin. "Doctors and patients cannot assume that the safety and efficacy of biosimilars are similar to the innovator epoetin because the biosimilars received marketing authorization," Singh stressed. In contrast to conventional medicines, which are manufactured in a relatively straightforward method, biopharmaceuticals are synthesized from living cells through a highly complex manufacturing process. "That's why producing a generic version of a conventional medicinal product is relatively easy while manufacturing a biosimilar version of a complex biopharmaceutical, such as epoetin alfa, is extremely difficult," said Singh. The subtlest variation in any stage of the nine-month EPO manufacturing process may influence the drug's biological activity and, by implication, its safety and efficacy, according to Suresh Aravind, executive director of Johnson & Johnson Pharmaceutical Services in the US. "The process is the product," Aravind said. "If you change the process, you change the product." Aravind urged drug-regulatory agencies, particularly those in developing countries, to require submission of comprehensive safety data from companies applying for marketing approval of biosimilars. Singh called on health-care professionals to remain vigilant. "We must closely monitor the efficacy and safety of biosimilar epoetins to ensure patient safety." M
WASHINGTON A shot of sildenafil (Viagra) may one day help shift workers and flight crews recover their normal sleep cycles. Sildenafil could be "useful in other circadian disorders that involve poor synchronization with the environment, including delayed-sleep-phase syndrome and adaptation to changing light schedules," said a study published in the Proceedings of the National Academy of Sciences in May. Researchers at Argentina's National University at Quilmes in Buenos Aires injected male hamsters with small amounts of the drug and switched off the lights six hours earlier, which researchers compared with taking an eastbound flight, as would occur from the Americas to Europe. Hamsters receiving a dose of the drug adapted 20 to 50 percent more quickly to the new schedule than hamsters receiving a placebo, the study said, as judged by how quickly they resumed running on their exercise wheels. However, the trick worked only when moving the schedule ahead, as on the so-called eastbound change, without helping hamsters shifted six hours in the other direction. Mammals, such as humans and hamsters, regulate their circadian rhythms by releasing chemicals in the brain, such as melatonin. However, repeated injections of melatonin are required to achieve a shift in sleep-wake cycles, compared with the single-dose effectiveness of sildenafil. The drug interferes with an enzyme that reduces the levels of cyclic guanine monophosphate in the brain, which helps regulate circadian rhythm, the body's inner clock. M AFP |
