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Topical Metformin Absorption

Drug Absorption - Clinical Pharmacology - Merck Manuals Professional Edition

Drug Absorption - Clinical Pharmacology - Merck Manuals Professional Edition

(See also Overview of Pharmacokinetics .) Drug absorption is determined by the drugs physicochemical properties, formulation, and route of administration. Dosage forms (eg, tablets, capsules, solutions), consisting of the drug plus other ingredients, are formulated to be given by various routes (eg, oral, buccal, sublingual, rectal, parenteral, topical, inhalational). Regardless of the route of administration, drugs must be in solution to be absorbed. Thus, solid forms (eg, tablets) must be able to disintegrate and deaggregate. Unless given IV, a drug must cross several semipermeable cell membranes before it reaches the systemic circulation. Cell membranes are biologic barriers that selectively inhibit passage of drug molecules. The membranes are composed primarily of a bimolecular lipid matrix, which determines membrane permeability characteristics. Drugs may cross cell membranes by Sometimes various globular proteins embedded in the matrix function as receptors and help transport molecules across the membrane. Drugs diffuse across a cell membrane from a region of high concentration (eg, GI fluids) to one of low concentration (eg, blood). Diffusion rate is directly proportional to the gradient but also depends on the molecules lipid solubility, size, degree of ionization, and the area of absorptive surface. Because the cell membrane is lipoid, lipid-soluble drugs diffuse most rapidly. Small molecules tend to penetrate membranes more rapidly than larger ones. Most drugs are weak organic acids or bases, existing in un-ionized and ionized forms in an aqueous environment. The un-ionized form is usually lipid soluble (lipophilic) and diffuses readily across cell membranes. The ionized form has low lipid solubility (but high water solubilityie, hydrophilic) and high electri Continue reading >>

Insulin And Metformin: Old Drugs, New Tricks

Insulin And Metformin: Old Drugs, New Tricks

Insulin and Metformin: Old Drugs, New Tricks Some pharmaceutical companies are developing new formulations of older medications to create new possibilities. Diabetes treatment is one area ripe for such disruption, as the incidence of diabetes will only increase in the coming years and prove to be a fruitful health care market. Taking that into consideration, diabetes treatments such as metformin and insulin are being targeted for innovation by certain players looking to capitalize on this trend. Pharmacists recognize that metformin is often a first-line agent for diabetes management, but its commonly experienced gastrointestinal (GI) side effects may discourage patient adherence. In light of this, several compounding pharmacies across the United States have started to create transdermal metformin products for their patients. Although transdermal metformin therapy is not necessarily a new invention, it has been generating some buzz for its potential large-scale application because it reduces GI side effects in patients by bypassing the GI tract. Westchase Compounding Pharmacy in Tampa, Florida, has actually patented the transdermal delivery of metformin therapy (US20120283332). The selling point is that patients only use approximately 10% of the usual dosage of metformin and apply anywhere from 50 mg to 200 mg topically to the inner wrists twice daily. Although a patent exists for transdermal metformin and other companies are exploring its use, the FDA has not approved the product, so we cant expect it to show up on our shelves anytime soon. An even larger market at play is insulin. Many pharmacists are familiar with patients fears of starting insulin therapy, which commonly stems from their fear of injecting it. With that in mind, several companies are looking to creat Continue reading >>

Metformin Without The Misery

Metformin Without The Misery

What if you could get all the benefits of metformin, but without the abdominal pain, diarrhea, gas, and vomiting that this medicine often brings? Well, such a treatment exists, and it works. Why hasnt it come to market? A group of enterprising osteopaths and pharmacists at Scarbrough Pharmaceutical Innovations, LLC, in Akron, Ohio, have patented a transdermal metformin (TDM) formula, or metformin that absorbs through the skin. The prescribed dose is squeezed out of a syringe and rubbed into the skin, although it could also be made into a skin patch. One of these osteopathic doctors, Jay Shubrook, DO, has been good enough to explain the issues to me. TDM has the same benefits as oral metformin. It lowers insulin resistance, prevents dumping of glucose by the liver, encourages weight loss, and treats polycystic ovary syndrome (PCOS). This could benefit millions of people. Whenever I or others write about metformin on this site, we get dozens of comments , equally divided between This drug is wonderful, and This drug is awful. It tore up my stomach. Many people cant take it, or it makes their lives miserable. The Ohio researchers prepared and tested a mix of four different polymers, or gels that can deliver metformin through the skin into the blood. According to their patent application , One advantage of using transdermal metformin is its ability to bypass the gastrointestinal system. This allows the drug to not have the gastrointestinal side-effects associated with oral metformin. Another unexpected benefit is that metformin seems to be absorbed through the skin much more effectively than through the digestive system. Apparently, 50% to 90% of oral metformin is degraded in the intestines and brings no benefit. According to research, a person taking 1500 milligrams (mg) Continue reading >>

Us20120283332a1 - Transdermal Delivery Of Metformin - Google Patents

Us20120283332a1 - Transdermal Delivery Of Metformin - Google Patents

US20120283332A1 - Transdermal delivery of metformin - Google Patents US20120283332A1 US13504799 US201013504799A US2012283332A1 US 20120283332 A1 US20120283332 A1 US 20120283332A1 US 13504799 US13504799 US 13504799 US 201013504799 A US201013504799 A US 201013504799A US 2012283332 A1 US2012283332 A1 US 2012283332A1 Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.) Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.) Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) A61MEDICAL OR VETERINARY SCIENCE; HYGIENE A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES A61K31/00Medicinal preparations containing organic active ingredients A61K31/155Amidines (), e.g. guanidine (H2NC(=NH)NH2), isourea (N=C(OH)NH2), isothiourea (N=C(SH)NH2) A61MEDICAL OR VETERINARY SCIENCE; HYGIENE A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycero

The Low Down On Metformin And Vitamin B12 Deficiency

The Low Down On Metformin And Vitamin B12 Deficiency

So many women with PCOS are prescribed Metformin (an insulin-sensitizing drug) to manage their Polycystic Ovarian Syndrome. And for good reason too. Metformin has been shown to improve many aspects of PCOS, including weight loss, fertility and improved testosterone levels (1). But, it also leads to Vitamin B12 deficiency if used at high doses or for long periods of time. So, here’s what you need to know about Metformin and Vitamin B12 deficiency with PCOS. What is Metformin? As I have already mentioned, Metformin is an insulin sensitizing drug that is often prescribed for women withPCOS. It works by decreasing absorption of glucose through the intestines, lowering the amount of glucose produced by the liver and making the body more sensitive to the insulin that is being produced. The overall effect of Metformin use for PCOS is lowered testosterone levels, improved ovulation and fertility as well as a more regular menstrual cycle. This is all sounding good, right? Well, it is good although there are some nasty side effects. A full discussion on Metformin is not going to be dealt with now, though. I really want to hone in on Metformin’s effect of Vitamin B12 levels as this could be affecting you right now. A free 6 lesson course that has helped women with PCOS around the world learn how to see lasting changes in their PCOS symptoms. Ready to join? Vitamin B12 Vitamin B12 is a vitamin that is vital for the body’s functioning. It is important for red blood cell formation, neurological function and DNA formation. If you are deficient in this important vitamin, it could lead to anaemia and neurological problems. (including memory loss – something that I have seen cropping up more often in PCOS communities). (2) Metformin and Vitamin B12 Right, so this is where it gets Continue reading >>

Phase 1 Study Of The Effects Of Combining Topical Fda-approved Drugs On Age-related Pathways On The Skin Of Healthy Volunteers

Phase 1 Study Of The Effects Of Combining Topical Fda-approved Drugs On Age-related Pathways On The Skin Of Healthy Volunteers

You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Phase 1 Study of the Effects of Combining Topical FDA-approved Drugs on Age-related Pathways on the Skin of Healthy Volunteers The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. ClinicalTrials.gov Identifier: NCT03072485 Information provided by (Responsible Party): Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information This is a phase 1 study in healthy adult volunteers to examine the effects of 3 FDA approved medications on skin aging when applied in topical form. This is an open label, placebo controlled study. Drug: Sirolimus Drug: Metformin Drug: Diclofenac The primary endpoint of the study is the profile of differences in transcript levels of age-associated genes such as those in the lamin-A, insulin like growth factor (IGF) and NFKB pathways as well as noncoding RNAs in topical agent-exposed arm skin versus placebo exposed arm skin in healthy volunteers. The secondary endpoints include (1) differences in skin wrinkling using a 4 point Likert scale for wrinkle severity between placebo and topical agent exposed arm skin after 4 weeks of usage; (2) the type and severity of adverse events, both systemic and skin localized after exposure to both topical agent and placebo vehicle cream. Phase 1 Study of the Effects of Combining Topical FDA-approved Drugs on Age-related Pathways on the Skin of Continue reading >>

Metformin Acne Treatment

Metformin Acne Treatment

Metformin is an anti-hyperglycemic drug used to treat patients with type 2 diabetes and to treat women with polycystic ovary syndrome (POCS) and hirsutism, excessive or unwanted facial or body hair. Metformin also has benefits in treating acne in patients with hyperandrogenism or excessive production of androgen. Hyperandrogenenism causes acne vulgaris, which is the increased accumulation of oil and bacteria in the skin pores and the formation of papules, pustules or nodules. Video of the Day Metformin was approved by the Food and Drug Administration (FDA) in 1995 only for the treatment of type 2 diabetes. According to the Northwestern University website, metformin is not FDA approved to treat POCS symptoms. However, treatment with metformin benefits women suffering with POCS because of its effect in reducing insulin, testosterone and glucose levels. These effects help to reduce the symptoms of acne, hirsutism, abdominal obesity and amenorrhea that are all symptoms of POCS. Metformin Effects on Acne Metformin is used to treat acne in specific conditions such as PCOS, which causes serious hormonal imbalances that cause acne outbreaks. Metformin works to balance the hormones and control the acne outbreaks. The side effects of metformin include gastrointestinal symptoms of nausea and vomiting, abdominal bloating and diarrhea. These symptoms may be minimized by starting with a low dosage that is gradually increased over a few weeks. Metformin will also affect the absorption of vitamin B12; long-term treatment with metformin may lead to anemia. A rare and serious side effect of metformin is lactic acidosis, too much acid in the body. Therefore, it’s important to have a serum creatinine test prior to starting metformin therapy and to have liver enzymes levels monitored ever Continue reading >>

Metformin Topical Cream Metformin Compound Atlanta Compounding - Pavilion Compounding Pharmacy

Metformin Topical Cream Metformin Compound Atlanta Compounding - Pavilion Compounding Pharmacy

TRANSDERMAL METFORMIN THERAPY TMT : AVOID UNWANTED SIDE EFFECTS Metformin is an effective FDA approved drug that is used as a first line therapy to treat patients with Type II diabetes. Metformin may also be used to prevent the development of diabetes in people at risk, for treatment of polycystic ovaries (PCOS), and for weight gain due to medications used for treating psychoses. Unfortunately for the 10 million people across the U.S. who are taking metformin tablets, 1 in 3 will experience uncomfortable side effects such as nausea, vomiting, gas, bloating, and diarrhea. These intolerable side effects often lead to a discontinuation of therapy. Here at Pavilion Compounding Pharmacy, located in Atlanta Georgia, we have been working with several healthcare providers to create a solution to reduce or eliminate many of the undesirable side effects of metformin. Using our formulation expertise, we have been able to take metformin USP powder and incorporate it into a transdermal base, Lipoderm, that can be applied topically. According to many recent studies, transdermal metformin is an effective alternative for patients who cannot tolerate the oral dose or cannot swallow the large tablets. The transdermal option allows the drug to be absorbed into the body while bypassing the gastrointestinal system and thus avoiding many of the unpleasant side effects. Another advantage of using transdermal metformin therapy is that a patients dose is generally only 10% of the oral dose. For example, if a patient was taking one 500mg tablet twice daily, they would only need to apply 50mg twice daily of the transdermal metformin. The current literature supports a dose of 50mg applied topically twice daily to the inner wrist. This dose can be titrated accordingly based upon patients blood glu Continue reading >>

Metformin - For The Dermatologist

Metformin - For The Dermatologist

We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Metformin though primarily an antidiabetic drug, has found to play an important role in a number of cutaneous disorders. Because of its role in improving hyperinsulinemia, it has proven beneficial in hormonal acne, hidradenitis suppurativa (HS) and acanthosis nigricans. Its antiandrogenic properties further serve as an add-on to the conventional management of hirsutism associated with polycystic ovarian syndrome. Very recently, systemic usage of metformin for psoriasis and cutaneous malignancies has shown promising results. Interestingly, metformin has also been topically used in hyperpigmentary disorders with pertinent levels of improvement and happens to be the most recent addition to the list of dermatologic indications. Though an oral hypoglycemic agent to begin with, metformin today has proven to be a boon for dermatologists. KEY WORDS: Hyperandrogenism, hyperinsulinemia, hyperpigmentary disorders, metformin, skin cancer (dimethylbiguanide) today is a widely used drug prescribed for diabetic patients. The history of metformin dates back to the usage of the herb Galega officinalis. This herb was found to be rich in a substance called guanidine with blood-glucose-lowering properties, which later was discovered to be the chemical basis of metformin. Though an antidiabetic drug to begin with, metformin has proven to be a drug of importance, in a number of cutaneous indications. Th Continue reading >>

Equine Insulin Resistance Metformin (glucophage)

Equine Insulin Resistance Metformin (glucophage)

You should AVOID this drug in horses for several reasons: 1. Equine Insulin Resistance is high Insulin levels with normal Glucose levels. But Metformin is a human Diabetes drug that has one job – to lower Glucose. It makes no sense to give a drug to lower Glucose in a horse with already normal Glucose. Metformin is for Type 2 Diabetes which most horses never get. Click here – Does my horse have Horse Diabetes? 2. Oregon State’s Veterinary Research Team in May 2009 found this drug is not absorbed by horses. It is going in one end and out the other and so is your time and money. Conclusions of the Study: only 4-7% of Metformin giving orally 2 times a day is absorbed and is “insufficient to achieve plasma concentrations of drug comparable to the therapeutic range achieved by humans.” AJVR 2009, May, Dr. Hustace. Click here to see article Pharmacokinetics and bioavailability of meformin in horses. 3. Metformin had no effect on Insulin Sensitivity in horses. K. Tinsworth, Australian Science Symposium, 2010. Click here to see article Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies. 4. Dr. Pratt, Professor at North Carolina State Universtiy, College of Vet. Med., stated, “Human drugs like Metformin have not proven to be effective in horses.” Morris Animal Foundation. 5. “Metformin is not an effective long-term mono therapy for increasing Insulin sensitivity in horses.” M. Vick, University of Kentucky Dept. of Vet. Sci, Reprod. 2006. Click here to read Dr. Vick’s study 6. No FDA approval for use in horses – creates liability issues. 7. One small study in England, years ago, thought they saw effect, but no university or institute can replicate these findings. This study was before Oregon State’s Veterinary School fou Continue reading >>

Mathematical Model-based Accelerated Development Of Extended-release Metformin Hydrochloride Tablet Formulation

Mathematical Model-based Accelerated Development Of Extended-release Metformin Hydrochloride Tablet Formulation

, Volume 17, Issue4 , pp 10071013 | Cite as Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation Research Article Theme: Leveraging BCS Classification and in-silico Modeling for Product Development Theme: Leveraging BCS Classification and in-silico Modeling for Product Development A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling Continue reading >>

Timing Your Metformin Dose

Timing Your Metformin Dose

The biggest problem many people have with Metformin is that it causes such misery when it hits their stomachs that they can't keep taking it even though they know it is the safest and most effective of all the oral diabetes drugs. In many cases all that is needed is some patience. After a rocky first few days many people's bodies calm down and metformin becomes quite tolerable. If you are taking the regular form of Metformin with meals and still having serious stomach issues after a week of taking metformin, ask your doctor to prescribe the extended release form--metformin ER or Glucophage XR. The extended release form is much gentler in its action. If that still doesn't solve your problem, there is one last strategy that quite a few of us have found helpful. It is to take your metformin later in the day, after you have eaten a meal or two. My experience with metformin--and this has been confirmed by other people--is that it can irritate an empty stomach, but if you take it when the stomach contains food it will behave. There are some drugs where it matters greatly what time of day you take the drug. Metformin in its extended release form is not one of them. As the name suggests, the ER version of the pill slowly releases the drug into your body over a period that, from my observations, appears to last 8 to 12 hours. Though it is supposed to release over a full 24 hours, this does not appear to be the case, at least not with the generic forms my insurer will pay for. Because there seems to be a span of hours when these extended release forms of metformin release the most drug into your blood stream, when you take your dose may affect how much impact the drug has on your blood sugars after meals or when you wake up. For example, the version I take, made by Teva, releases Continue reading >>

What Are The Possible Side Effects Of Glipizide And Metformin (metaglip)?

What Are The Possible Side Effects Of Glipizide And Metformin (metaglip)?

METAGLIP™ (glipizide and metformin HCl) Tablets 2.5 mg/250 mg 2.5 mg/500 mg 5 mg/500 mg DESCRIPTION METAGLIP™ (glipizide and metformin HCl) Tablets contain 2 oral antihyperglycemic drugs used in the management of type 2 diabetes, glipizide and metformin hydrochloride. Glipizide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea. Glipizide is a whitish, odorless powder with a molecular formula of C21H27N5O4S, a molecular weight of 445.55 and a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide. The structural formula is represented below. Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C4H12ClN5 (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown: METAGLIP (glipizide and metformin) is available for oral administration in tablets containing 2.5 mg glipizide with 250 mg metformin hydrochloride, 2.5 mg glipizide with 500 mg metformin hydrochloride, and 5 mg glipizide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, crosc Continue reading >>

Acute Renal Failure Related To Topical Acyclovir

Acute Renal Failure Related To Topical Acyclovir

Acute renal failure related to topical acyclovir Acute renal failure related to topical acyclovir Acute renal failure related to topical acyclovir Is it common to see renal failure triggered by high doses of topical acyclovir (Zovirax) (i.e., 800 mg five times a day)? The patient in question was obese, diabetic and hypertensive. Other medications include lisinopril (Zestril) 40 mg daily, metformin (Fortamet, Glucophage, Glumetza, Riomet) 1,000 mg b.i.d., and aspirin for pain. The last creatinine kinase level was 1.3 U/L. David Laubenstein, RPAC, Fayetteville, N.Y. High-dose parenteral acyclovir has long been known to be a cause of acute renal dysfunction, particularly if a patient does not remain well hydrated or experiences volume contraction. Some data show that high-dose oral regimens particularly those for varicella zoster virus (VZV) manifestations in the elderlymay exacerbate renal dysfunction, but this documentation is less extensive than that for parenteral therapy. Drug-induced nephrotoxicity appears to be attributed to renal tubular damage caused by acyclovir-induced crystalluria (Pathol Lab Med. 2002;126:753-754). Topical acyclovir is available by prescription as a 5% cream and a 5% ointment. Applying roughly 0.5 inches (0.5 g of product) to a 4.5 in2 area of skin normally delivers approximately 25 mg of acyclovir. The topical cream is available in 2-g and 5-g tubes that contain only 100 mg and 250 mg of active drug, respectively. The ointment formulation is available in a 30 g tube that contains 1,500 mg of active drug. Systemic absorption of topical acyclovir is poor. Several pharmacokinetic studies conducted by the manufacturer have demonstrated a minimal amount of systemic exposure following application, with many healthy subjects having undetectable lev Continue reading >>

Topical/transdermal Metformin Cream

Topical/transdermal Metformin Cream

If this is your first visit, be sure tocheck out the FAQ by clicking thelink above. You may have to register before you can post: click the register link above to proceed. To start viewing messages,select the forum that you want to visit from the selection below. So I've been having issues with a lot of stomach problems when i was on 500/mg twice a day of regular instant release metformin. I did a lot of research and came across some pharmacies/patents talking about a transdermal topical cream application of metformin. I went to a compounding pharmacy and they created it and the dose being 200mg (100 mg twice a day). The small studies they have done say that 10% of the oral dose is supposed to be sufficient when using it transdermal instead of orally. Does ANYBODY have any experience with this, or know about anybody who did it this way? If so, what dose are you on? Did it work for you? Did you go back to oral medication? I have only been on the cream for two days. I apply it to my wrists. It takes a while to absorb and after leaves a sticky residue and shiny residue. Today i happened to go drive afterwards and the cold ac in my car turned the residue white. I dont know if its not absorbing or if this is normal. Scared its not going to work and that ill put the 12 pounds i lost back on, and then have to go back on the oral medication and start the whole cycle of adjusting to the horrible stomach aches over. Please give me any input you can, it would be much appreciated. Take care, and ill keep you guys posted if i stick with it and find any information out! By the way, compounding pharmacies in my area (southern california) charge 65-75 for a month supply of 200/mg a day. Continue reading >>

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