Figure 5. The effects of a two-fold increase in the volume of distribution of a drug on its plasma concentration-time profile after the oral administration of the drug. The kinetic parameters used for simulation are CL of 1.16 L h, V of absorption rate constant of 1 hr -1 , and F of 1 for the "Normal V" scenario. V was increased to 20 L for the "Increased V" scenario.
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Page 13 1 2 Sec. 37. Section 99F.4A, subsection 8, Code 2003, is amended by striking the subsection and inserting in lieu thereof the following: 8. The commission shall, upon the immediate payment of the applicable table games license fee and submission to the commission by June 1, 2005, of an application by a licensee of a pari-mutuel dog or horse racetrack licensed to conduct gambling games at a pari-mutuel racetrack enclosure, issue a license to the licensee to conduct table games of chance, including video machines that simulate table games of chance, at the pari-mutuel racetrack enclosure subject to the requirements of this subsection. However, a table games license may only be issued to a licensee required to pay a table games license fee of three million dollars under this subsection if the licensee, and all other licensees of an excursion gambling boat in that county, file an agreement with the commission authorizing the granting of a table games license under this subsection and permitting all licensees of an excursion gambling boat to operate a moored barge as of a specific date. The licensee shall be granted a table games license by the commission without conducting a separate referendum authorizing table games upon payment of the applicable license fee to the commission which table games license fee may be offset by the licensee against taxes imposed on the licensee by section 99F.11, to the extent of twenty percent of the table games license fee paid pursuant to this subsection for each of five consecutive fiscal years beginning with the fiscal year beginning July 1, 2008. Fees paid pursuant to this subsection are not refundable to the licensee. A licensee shall not be required to pay a fee to renew a table games license issued pursuant to this subsection. Moneys collected by the commission from a table games license fee paid under this subsection shall be deposited in the rebuild Iowa infrastructure fund created in section 8.57. For purposes of this subsection, the applicable license fee for a licensee shall be three million dollars if the adjusted gross receipts from gambling games for the licensee in the previous fiscal year was less than one hundred million dollars, and shall be ten million dollars if the adjusted gross receipts from gambling games for the licensee in the previous fiscal year was one hundred million dollars or more. Sec. 38. Section 99F.5, subsection 1, Code 2003, is amended to read as follows: 1. A qualified sponsoring organization may apply and penicillin.
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Able is their opinion of the requirements that the U.S. Department of Health and Human Services DHHS ; had proposed a couple of years ago for the discount drug card that it wanted Medicare to offer. Only PBMs could have offered such a card; however, a lawsuit, filed by the National Association of Chain Drug Stores NACDS ; and the National Community Pharmacists Association, kept that version of the card from coming to fruition. The discount drug card that the Medicare conferees are anticipating is not as PBM-oriented. Paul Kelly, vice president of federal legislative affairs for NACDS, emphasizes that the pharmacy access language is based on that of the military's Tricare insurance program. "It's not perfect, but it is better than nothing, " he explains. It is certainly better than what DHHS had wanted: PBMs would have had to include only one pharmacy for every 10mile radius within an area. Nonetheless, the congressional provision seems to tilt pretty heavily toward PBMs. For example, TogetherRx, a card of fered by a consor tium of manufacturers, could not qualify, because its card is of fered only to low-income Medicare recipients. In addition, card companies would not have to pass along the entire discount--or even a fixed percentage of it--that they negotiate with drug manufacturers. Nothing in the provision would preclude a company from dropping a drug from its formulary. The House and Senate conferees working on the Medicare bill were putting their finishing touches on their Medicare drug card provision just as the General Accounting Office GAO ; was publishing a generally positive report on PBM cards. The report examined the multiple card programs run by Medco Health Solutions formerly Merck Medco Managed Care ; , AdvancePCS, Express Scripts, and WellPoint Health for their customers and compared them with cards offered by Eli Lilly, GlaxoSmithKline, Novartis, and Pfizer as well as TogetherRx on its Web site. To no one's surprise, the manufacturers' cards offer lower prices for their own drugs than those offered by PBMs. Of course, however, a Medicare recipient would have to obtain cards from numerous manufacturers; the manufacturers' cards don't help when patients buy generic dr ugs, and the cards are available only to low-income elderly adults. The PBM cards are broadly available and yield considerable savings. The GAO examined prices for nine drugs in three cities: atenolol e.g., Tenormin, AstraZeneca ; , celecoxib Celebrex, Pharmacia ; , alendronate Fosamax. Merck ; , furosemide Lasix, Aventis ; , atorvastatin Lipitor, Pfizer ; , amlodipine besylate Norvasc, Pfizer ; , conjugated estrogens Premarin, Wyeth-Ayerst ; , omeprazole Prilosec, AstraZeneca ; , and simvastatin Zocor, Merck ; . A PBM-administered card for pharmacies within the Washington, DC, area resulted in median savings ranging from $2.09 to $20.95 for each of the nine drugs. Savings elsewhere were similar. If nothing else, then, it behooves Congress to get a national drug discount card system in place. Such a step would increase competition among PBMs based on prices to consumers. Everyone would benefit, not just our parents and grandparents. I Stephen Barlas is a freelance writer based in Washington, DC, who covers issues inside the Beltway. Send ideas for topics and your comments to sbarlas bellatlantic.
ABSORPTION AND TISSUE DISTRIBUTION OF THE CITRUS FLAVANONE NARINGENIN. J. Marks1, M. Mohsen4, G. Kuhnle4, C. Rice-Evans4, K. Moore3, G. Gibson5, E.S. Debnam1 and S.K. Srai2. Departments of 1Physiology; 2Biochemistry & Molecular Biology and 3Centre for Hepatology, Royal Free & University College Medical School, London; 4Antioxidant Research Group, King's College, London. 5School of Food Biosciences, University of Reading, Reading, UK. J. Physiol. Biochem., 60 2 ; , 175, 2004. Citrus flavonoids are reported to have anti-inflammatory and anti-carcinogenic effects. However, little information is known about the gastrointestinal uptake and subsequent tissue distribution of these flavonoids. This present study determined the extent of absorption of naringenin across the rat GI tract and the distribution of the flavonone and its metabolites in heart, lungs, small intestine, colon, brain, liver, kidneys and spleen. Following a 4 h fast, Sprague-Dawley rats 250 g ; were gastric gavaged with 10 or 50 mg kg [3H]-naringenin. Animals were anaesthetised at 2 h post-gavage, 2ml of blood was removed by cardiac puncture and the animal exsanguinated using ice-cold heparinised 0.9% saline. Tissues were removed, weighed and homogenised in 0.9% saline and [3H] activity determined by scintillation counting. Identical experiments used unlabelled naringenin and in this case extracts from homogenised tissues were analysed by HPLC, LC-MS and GCMS to allow identification and quantification of naringenin and its metabolites. Uptake of [3H]-naringenin at 2 h and 18 h averaged 47% and 87% respectively of the gavaged dose. Naringenin was detectable in all tissues examined but was present at greatest levels in plasma, urine and faeces. At 2 h relatively little activity was detected in small intestinal tissue 1.62% and 0.86% of that gavaged using 10 and 50mg kg, respectively ; indicating efficient efflux to blood. The glucuronides were the major forms in plasma and tissues at 2 h post-gavage, but after 18 h the predominant form in tissues, particularly the brain and lungs was the aglycone. The colonic metabolite 3- 4-hydroxyphenyl ; propionic acid was detected in urine and faeces and accounted for 14.7% and 67.4% respectively of total naringenin metabolites after 18 h. These data indicate that the GI tract and peripheral tissues are important for the metabolism of ingested naringenin. We are grateful to the Food Standards Agency for support Contract No. T01020 and phenergan.
The american journal of medicine, volume 108, issue 4, pages 343-345 bodey to view this article, please choose one of your preferred elsevier websites: access to the full-text of this article will depend on your personal or institutional entitlements.
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