"Denosyl (S-Adenosylmethionine)" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 8; March 1, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! ANNOUNCEMENTS 1 - Come Celebrate! We're having a Celebration of Life reception Saturday March 23rd at Gulf Coast Veterinary Oncology from 2-5 pm. Bring a picture of your pet to place in our new display case. Sorry, no pets allowed since we will be celebrating in our Deli. 2 - Free chemotherapy for relapse lymphoma! Beginning April 1st, we will be offering a free chemotherapy trial for dogs with previously treated lymphoma at our Houston Office. 3 - Free chemotherapy for lymphoma! Beginning April 15th, we will be offering a free chemotherapy trial for dogs diagnosed but previously untreated lymphoma at our Houston Office. 4 - Are you an RVT living in the Houston area and want to work for us! Call Dr. Hahn or Ms. Rhonda Dailey (713-693-1166) for more information. Great Benefits, 4 day work week, travel to a National Meeting every other year, and more! These are exciting times for us at Gulf Coast Veterinary Oncology - Please call us (Drs. King, Hahn, Cerraras, Freeman & Turner) at any time and check our web site regulary for more information! ====================================================== THIS WEEK'S TUMOR TIDBIT: Denosyl (S-Adenosylmethionine) WHAT THE TEXTBOOKS SAY: Denosyl SD4 is the patented, pure and stabilized 1,4-butanedisulfonate salt of S-Adenosylmethionine for veterinary use only. It is the only brand of S-Adenosylmethionine researched in U.S. trials for veterinary use in dogs and cats. Denosyl SD4 is available in two strengths: as an enteric coated 90 mg and 225mg tablet of active S-Adenosylmethionine. Because S-Adenosylmethionine is extremely hygroscopic, tablets are individually sealed in foil blister packs. Background S-Adenosylmethionine is an endogenous molecule synthesized by cells throughout the body. Formed from the amino acid methionine and ATP, S-Adenosylmethionine is an essential part of three major biochemical pathways: transmethylation, transsulfuration and aminopropylation. As part of these pathways, S-Adenosylmethionine is essential to all cells and is particularly important in hepatocytes because of their central role in metabolism. Deficiency of S-Adenosylmethionine has been associated with a spectrum of cellular derangements that have profound effects on hepatocytes, and in fact there is evidence that a deficiency of S-Adenosylmethionine in the body may initiate or contribute to abnormalities of cellular structure and function in many body tissues, including the liver. Conversely, exogenous administration of S-Adenosylmethionine has been shown to result in improvements in hepatocellular function in both in-vivo and in-vitro studies, without cytotoxicity or significant side effects. Precursors of S-Adenosylmethionine do not have similar effects. Administration of large amounts of methionine has no beneficial effect on S-Adenosylmethionine levels and may be toxic. The only way to increase S-Adenosylmethionine levels is by direct supplementation with S-Adenosylmethionine. Purpose Denosyl SD4 has been shown to increase hepatic glutathione levels in cats and dogs. Glutathione is a potent antioxidant that protects hepatic cells from toxins and death. A recent analysis of 31 dogs and cats with various severe liver problems showed that 45% of these animals had low hepatic glutathione levels. Denosyl SD4 is recommended to improve hepatic glutathione levels in compromised patients to help maintain and protect liver function. Denosyl SD4 may also be used in other conditions of tissue oxidant injury and RBC fragility caused by certain toxins or drugs which are related to reduced glutathione concentrations. Pharmacokinetics Pharmacokinetic studies in dogs administered enteric-coated tablets of the identical stabilized salt of S-Adenosylmethionine found in Denosyl SD4 have been completed. When this material is administered orally on an empty stomach, absorption was confirmed with peak absorption ranging from one to two hours. Co-administration of Denosyl SD4 and prednisone did not affect the bioavailability or pharmacokinetics of either substance. Safety Acute and chronic high-dose administration of the identical stabilized salt of S-Adenosylmethionine found in Denosyl SD4 demonstrated an exceptionally wide margin of safety. Oral acute toxicity studies in rats indicated an LD50 greater than 4,640 mg/kg. Clinically healthy cats administered Denosyl SD4 at greater than 4 times the recommended daily dose for 118 days remained healthy with no adverse changes in CBC, serum chemistries or liver histology. Administration as a Dietary Supplement Because the tablet must be kept intact to prevent destruction by stomach acid, administration utilizes a dosage range, based on the nearest whole-tablet dose. The chart below is provided as a guide for administration. Daily dosage may also be calculated, based on 18 mg/kg of body weight and rounded to the closest tablet size or combination of sizes. For optimal absorption, tablets should be given on an empty stomach, at least one hour before feeding, as the presence of food decreases the absorption of S-Adenosylmethionine. When giving more than one tablet, the total daily dose may be provided as a morning and evening dose. For example, a daily dose of three tablets could be divided into two tablets in the morning and one tablet in the evening. FELINE AND CANINE DENOSYL SD4 ADMINISTRATION GUIDE Body weight Total daily administration and tablet size Up to 12 pounds (5.5 kg), One tablet of 90 mg 12 to 25 pounds (5.5-11 kg), Two tablets of 90 mg 25 to 35 pounds (11 -16 kg), One tablet of 225 mg 35 to 65 pounds (16 - 29.5 kg), Two tablets of 225 mg Over 65 pounds (29.5 kg +), Three tablets of 225 mg The number of tablets can be gradually reduced or may be increased at any time depending on the pet's needs. Storage Store in a cool dry place. Keep tablets in original blister pack until used. Tablets are sensitive to moisture and extreme heat and should not be split or crumbled. WHAT DO WE DO AT GULF COAST? Antioxidants such as those that promote an increase in intracellular glutathione can be used safely during chemotherapy or radiotherapy in pets with cancer. We commonly use the antioxidant CoQ10 during Adriamycin (doxorubicin) therapy for its cardioprotective effects and use Hepatosupport (an multinutrient supplement) for its liver protective effects. Denosyl is available from Nutramax and CoQ10/Hepatosupport is readily available from RxVitamins.com. Don't hesitate to call or email us at Gulf Coast Veterinary Oncology! ALL THE BEST, Kevin A. Hahn, DVM, PhD Diplomate ACVIM (Oncology) & Overall Nice Guy Gulf Coast Veterinary Specialists 1111 West Loop South, Suite 150 Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 http://www.gcvs.com mailto:drhahn@gulfcoastvetspec.com