DHT rebound minimal after missed 5-ARI doses


San Francisco--Because of its longer half-life, dutasteride (Avodart) may confer an advantage not seen with finasteride (Proscar), according to UCLA researchers. Missed doses of dutasteride, a newer 5-alpha-reductase inhibitor, are not likely to impact drug-induced suppression of dihydrotestosterone (DHT), and clinically that difference may be important because BPH patients often miss doses of prescribed medicines.

"A patient who forgets to take his dutasteride is not going to experience DHT rebound, like a patient who misses doses of finasteride," said Leonard Marks, MD, associate professor of urology at UCLA and medical director of the Urological Sciences Research Foundation. "This raises the possibility that a new formulation of the drug could be developed, one that required, for example, only weekly dosing."

Dr. Marks drew his conclusions from a study he conducted with researchers from the University of Texas Southwestern, Dallas, and GlaxoSmithKline. He presented their findings at the AUA annual meeting.

The dutasteride patients started with a mean DHT level of 402.5 pg/mL. By day 28, mean DHT level dropped to 37.5 pg/mL. Finasteride patients started with a mean DHT level of 502.3 pg/mL, which had dropped to 116.1 pg/mL after the 28-day regimen.

A week after ceasing therapy, dutasteride patients still maintained their lower DHT level-a mean of 38.3 pg/mL-compared with the finasteride patients whose DHT levels climbed to a mean of 324.8 pg/mL a week after therapy ended. Overall, dutasteride maintained a 90.1% reduction for that week, compared with a 35.2% reduction for finasteride. Placebo patients experienced a negligible reduction in DHT.

Studies have shown that missed doses may negatively affect patients' health, and many patients allow gaps between their prescriptions of BPH drugs (Clin Pharmacol 2001; 6:47; Eur Urol 2003; 44:539). Dr. Marks said the results could be explained by the differences in half-life of the two drugs-5 weeks for dutasteride compared with 6 to 8 hours for finasteride.

Dosage of less than once/daily? This study raised the question whether dutasteride could be taken less often than once daily. Dr. Marks responded that DHT suppression is dose-dependent. At 24 weeks, 0.01 mg/day of dutasteride produces less than a 10% reduction in DHT. At the same time point, a 0.1 mg/day dose causes about a 50% reduction in DHT. A weekly dose of dutasteride, 3.5 mg, produces a DHT of about 20 ng/mL, which is close to the level caused by a 0.5-mg daily dose.

The results, said Dr. Marks, imply that missing a dose of dutasteride has less effect on blood levels of DHT than missing a dose of finasteride. He also cautioned against intermittent dosing with 0.5 mg of dutasteride, as the clinical implications of this have not been studied. Until such clinical trials are conducted, he emphasized that clinicians should continue using the drug according to approved labeling.

The study is an interesting first step, said Steven A. Kaplan, MD, professor of urology and vice chairman of urology of the College of Physicians and Surgeons at Columbia University.

"There are already people who [intentionally] take these medicines intermittently and claim to have the same effect," he said. "But that's just anecdotal."

Studies like this one will help to determine whether this approach can really work, Dr. Kaplan said, adding that more needs to be known before clinicians change their prescriptions.

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