Nov 9, 2006 (CIDRAP News) – A laboratory study indicates that the antiplatelet drug clopidogrel (Plavix) may limit the action of the antiviral oseltamivir (Tamiflu), which could mean trouble for cardiovascular disease patients who contract influenza.The study by a team from the University of Rhode Island suggests that people taking clopidogrel to prevent heart attack or stroke may get little benefit from oseltamivir. The team found that clopidogrel reduced an initial step in the metabolization of oseltamivir up to 90% when the drugs were present in equal concentrations, according to the study, published in the Journal of Pharmacology and Experimental Therapeutics.”Concurrent use of both drugs would inhibit the activation of oseltamivir . . . thus making this antiviral agent therapeutically inactive,” said senior author and pharmacy professor Bingfang Yan in a University of Rhode Island news release.However, it’s not known whether the drug interaction observed in the lab study would occur to the same extent in the human body, according to others, including a spokesman for Roche, the manufacturer of Tamiflu.Oseltamivir, a neuraminidase inhibitor, is used to treat seasonal flu and is both the first-choice drug for treating people infected with H5N1 avian influenza and the best hope for treatment if H5N1 evolves into a pandemic strain. It must be given within the first 48 hours of symptom onset to be effective. Clopidogrel is used widely to prevent heart attack and stroke in patients who have already had such an episode or have peripheral arterial disease.Oseltamivir must first be hydrolyzed (split into fragments by reaction with water) to be active in the body, according to the report. The researchers report that a liver enzyme called HCE1 is a key factor in the hydroloysis of both oseltamivir and clopidogrel. The scientists induced human embryonic kidney cells to produce HCE1, exposed the cells to high-frequency sound, and used a centrifuge to remove the cell debris, their report says. Then they added varying amounts of oseltamivir and clopidogrel to the remaining liquid and assessed the hydroloysis of oseltamivir.When clopidogrel and oseltamivir were present in equal concentrations of 50 micromoles per liter, hydrolysis of oseltamivir was reduced by up to 90% compared with the level in the absence of clopidogrel. When the concentration of clopidogrel was only 10% that of oseltamivir, it still reduced hydrolysis of the antiviral by 55%, according to the report.Given the widespread use of clopidogrel, it is likely that oseltamivir and clopidogrel are used concurrently in some patients, the report states. The findings suggest that those who receive both drugs at the same time remain susceptible to flu if they are not yet infected or, if they are infected, can spread it to others, the authors say.”Now we need to study the effects of the combination in human trials,” Yan said in the news release. He has notified the US Food and Drug Administration and the National Institutes of Health of his findings.Louis M. Mansky, director of the University of Minnesota’s Institute for Molecular Virology in Minneapolis, said the findings warrant further study to see if the drug interaction would occur in the human body as it does in the laboratory.”The study is interesting and suggests that Plavix can prevent metabolic conversion of Tamiflu to the active drug,” Mansky told CIDRAP News by e-mail.”The main limitation is that it’s unclear how well this finding translates into a clinical situation (ie, it might not be as concerning, as the inhibition of Tamiflu conversion might not be as great),” he said.”Observations in cell culture don’t always translate perfectly when analyzed in clinical studies,” Mansky added. “The only way to know for sure is to extend these studies, which I think is warranted and worth doing.”Terence J. Hurley, a US spokesman for Roche, manufacturer of Tamiflu, said the study by itself does not prove there is a clinically relevant interaction between clopidogrel and oseltamivir.”Roche has made a preliminary review of this publication and concludes that the authors extrapolate their findings beyond the scope of the study,” Hurley told CIDRAP News by e-mail. “The clinical conclusions are made based on in vitro data from a limited dataset. Neither the limitations of the in vitro study nor the clinical relevance of concentrations evaluated were discussed.”He added that Roche plans to conduct a full evaluation of the study and will provide the results to regulatory agencies if any significant concerns are identified.Shi D, Yang J, Yang D, et al. Anti-influenza viral prodrug oseltamivir is activated by carboxylesterase HCE1 and the activation is inhibited by anti-platelet agent clopidogrel. J Pharmacol Exper Ther 2006; early online publication Sep 11 [Abstract]
He takes on Joe Perry in the final at Alexandra Palace in London.Perry secured his place with a 6-5 win over Barry Hawkins last night.
In any case, here’s some brain food to chew on while we wait for baseball to get in full gear and guys to sign.30 TEAMS, 30 GRADES:Which MLB club had the best offseason?Outfield: Bryce Harper2018 stats: 159 games, 34 home runs, .889 OPS (133 OPS+)The fact that Harper is even on this list is disturbing. He’s a 26-year-old All-Star who arguably has yet to enter his prime, won an MVP award in 2015 and was healthy in 2018, warding off injury concerns and woes that plagued him seemingly every other season.Outfield: Adam Jones2018 stats: 145 games, 15 home runs, .732 OPS (102 OPS+)Jones’ best days might be behind him, but he’s still only 32, hardly ancient in baseball. His double-digit home run power still plays, and it’s a safe bet that with a change of scenery, Jones might be an impact player for a new team.Outfield: Carlos Gonzalez2018 stats: 132 games, 16 home runs, .796 OPS (99 OPS+)Gonzalez has spent almost his entire career with the Rockies and will likely end it with another team. He has been an average defender throughout his career, and even though his power numbers have dipped the last two seasons (30 home runs combined in 2017 and 2018), he’s a serviceable player and a good starting outfielder.MORE: Justin Verlander speaks out on state of free agencyThird base: Mike Moustakas2018 stats: 152 games (54 with Milwaukee, 98 with Kansas City), 28 home runs, .774 OPS (108 OPS+)Moustakas played on a one-year deal in 2018 following the equally brutal 2017-18 offseason. The sad part is, Moustakas was coming off arguably his best year in 2017 (38 home runs, 117 OPS+) and still could only get a one-year offer. After another solid year, Moustakas is waiting to sign once again. His OBP has never been great — .307 career OBP (woof) — but his power is legit and he’s an average-ish defender.Shortstop: Manny Machado2018 stats: 162 games (96 with Baltimore, 66 with Los Angeles Dodgers), 37 home runs, .905 OPS (146 OPS+)What is there to say, really? Similar to Harper, it’s a disgrace that Machado doesn’t have a contract yet. Don’t blame the players for that. With baseball taking in record revenues, TV deals reaching astronomical values and a trip to the ballpark costing your first-born child, there’s no reason that teams can hide behind being broke anymore. Pay these guys.Regardless, Machado is on here for obvious reasons. You know, like being a 26-year-old superstar.Second base: Marwin Gonzalez2018 stats: 145 games, 16 home runs, .733 (103 OPS+)Gonzalez played a career-high 32 games at second in 2018, but it’s obvious he can play anywhere on the field and still be a decent defender. Utility players’ values are found usually more in their bat than their defense, and Gonzalez’s bat would play anywhere.MORE: The worst free-agent deals for all 30 MLB teamsFirst base: Logan Morrison2018 stats: 95 games, 15 home runs, .644 OPS (73 OPS+)The first-base options are dwindling, but it’s worth taking a flier on Morrison, who has double-digit home run power and hit 38 bombs in 2017. He’s also a decent defensive first baseman, coming off a 3 DRS season in 2018 with Minnesota. Morrison has a 103 career OPS+ and is only 31, so it might not be unfair to say you can wipe his 2018 off the map.Catcher: Martin Maldonado2018 stats: 119 games (41 with Houston, 78 with Los Angeles Angels), nine home runs, .627 OPS (73 OPS+)Maldonado is a light-hitting catcher — career 73 OPS+ — but he’s an above-average defensive catcher. Really, he can platoon with the other catcher on the team — Matt Wieters, below — to make for a pretty good backstop.Designated hitter: Evan Gattis2018 stats: 128 games, 25 home runs, .736 OPS (101 OPS+)”El Oso Blanco” has hit 20 or more home runs in five of six major league seasons and has a career 112 OPS+. He’ll bop for anyone, that’s for sure.MORE: The 15 worst MLB free-agent signings of all timeStarting pitcher: Dallas Keuchel2018 stats: 34 starts (204 2/3 innings), 3.74 ERA, 3.69 FIPIt’s pretty insane that Keuchel remains unsigned the second week in February. The 2015 Cy Young winner had another very good year in 2018, though he did lead the majors in hits allowed (211). Keuchel turned 31 this offseason, so it’s not as though he’s ancient, either. Keuchel allowed three runs or fewer in 25 of his 34 starts. He was pretty inconsistent in the latter stages of the season, but those numbers are still really good.Starting pitcher: Gio Gonzalez2018 stats: 32 starts (27 with Washington, five with Milwaukee), 4.21 ERA, 4.16 FIP. (With Washington: 4.57 ERA; with Milwaukee: 2.13 ERA)Gonzalez finished strong with the Brewers, including am 0.947 WHIP. That’s actually, like, very good.Starting pitcher: Clay Buchholz2018 stats: 16 starts (98 1/3 innings) 2.01 ERA, 3.47 FIPNo one expected Buchholz to do what he did with Arizona in 2018, so it’s both surprising and not that he hasn’t been offered a contract. Buchholz did have a 12.27 ERA with the Phillies in 2017, so maybe teams are apprehensive of which Buchholz will show up Starting pitcher: Edwin Jackson2018 stats: 17 starts (92 innings), 3.33 ERA, 4.65 FIPThe well-traveled Jackson had a very good year with the A’s; in fact, it was the best season of his career in a long time, even though it was abbreviated. Jackson would slot in well at the back end of a rotation.Starting pitcher: James Shields2018 stats: 34 games, 33 starts (204 2/3 innings), 4.53 ERA, 5.09 FIPAt this stage in his career, Shields, 37, is probably nothing more than a fifth starter. But he pitched to a 4.50 ERA in 204 innings as a starter last year. Teams can’t bank on ace-quality stuff, but they can bank on innings, and Shields is sure to deliver that.BenchJosh Harrison, utility2018 stats: 97 games, eight home runs, .656 OPS (80 OPS+)Harrison is coming off one of the worst offensive seasons of his career, but he’d still be a solid bat off the bench. He also doesn’t strike out much, which would be a big boon to a strikeout-heavy lineup.Derek Dietrich, utility2018 stats: 149 games, 16 home runs, .751 OPS (112 OPS+)Dietrich set a career high in home runs in 2018 and can play pretty much everywhere on the field. His defense suffers, but Carlos Gomez, outfielder2018 stats: 118 games, nine home runs, .634 OPS (76 OPS+)Gomez is coming off one of the worst offensive seasons of his career (his Minnesota years were pretty bad), hitting .208 with the Rays with just nine home runs. Gomez was a late signing last year, not officially with the club until March 3, so maybe that had something to do with his poor performance. In any case, Gomez’s track record is too good to have a hitter and defender like him coming off the bench.Matt Wieters, catcher2018 stats: 76 games, eight home runs, .704 OPS (86 OPS+)Wieters never really reached his potential as a franchise savior for Baltimore, between injuries and general ineffectiveness. He headed down the Beltway to Washington for two seasons, but the change of scenery didn’t really work. Wieters is still a solid defensive catcher, though; he threw out 37 percent of baserunners in 2018, 9 percent above league average.Relief pitcher: Craig Kimbrel2018 stats: 63 games, 62 1/3 innings, 42 saves, 2.74 ERA, 3.13 FIP Kimbrel is one of the premier relief pitchers in all of baseball. It’s February. He’s not signed. This is ridiculous.Relief pitcher: Adam Warren2018 stats: 47 games (24 with Yankees, 23 with Seattle), 51 1/3 innings, 3.14 ERA, 3.94 FIPWarren excelled as a seventh-inning guy for the Yankees, so maybe he can work as a bridge guy in the bullpen as well.Relief pitcher: Tony Sipp2018 stats: 54 games, 38 2/3 innings, 1.86 ERA, 2.41 FIP Sipp is your lefty out of the ‘pen, and he had an excellent year getting out lefties and righties in 2018.Relief pitcher: Ryan Madson2018 stats: 58 games (49 with Washington, nine with Los Angeles Dodgers), 52 2/3 innings, 5.47 ERA, 3.98 FIPMadson had a rough go of it in 2018, but the 38-year-old still has great velocity (96.4 mph average, per Fangraphs) and was excellent for Washington and Oakland in 2017. Relief pitcher: Tyler Clippard2018 stats: 73 games, 68 2/3 innings, 3.67 ERA, 4.24 FIPAfter a rough half-season with Houston in 2017, Clippard had a decent year out of the bullpen for the Blue Jays in 2018. Clippard allowed just two earned runs over his last 10 appearances last season.Relief pitcher: Nick Vincent2018 stats: 62 games, 56 1/3 innings, 3.99 ERA, 3.75 FIP Spring training may be here, but the market doesn’t seem to be thawing.For the second year in a row, free agency has slowed to a halt. While the crown jewel of last year’s offseason, J.D. Martinez, waited until Feb. 26 to sign, the fact that both Manny Machado and Bryce Harper find their names on this team on Feb. 13 is something of an embarrassment and a black eye on baseball. If you’re looking solely at the numbers, Nick Vincent has been one of baseball’s better relievers for a long time. He’s coming off a mediocre year with the Mariners, but prior to 2018 he pitched to a 2.95 FIP between San Diego and Seattle. He won’t blow anyone away with velocity, but he mixes his pitches and the breaking stuff is pretty good.Relief pitcher: Bud Norris2018 stats: 64 games, 57 2/3 innings, 3.59 ERA, 3.99 FIPNorris posted the lowest ERA in his career in 2018. Some of that is misdirection, though, since this was the first season he worked exclusively out of the bullpen. Some of Norris’ ERA was also inflated by a bad September.
The 23-year-old guard wasn’t willing to take all the credit, though. After Brooklyn’s 123-121 victory over Sacramento, Russell attributed the win to his teammates for allowing him to get open. Related News NBA wrap: Bucks hand Lakers fourth consecutive loss The Nets pulled off an unlikely win Tuesday against the Kings after being down 28 points in the second half — and the comeback came behind D’Angelo Russell’s strong night.Russell scored a career-high 44 points with 27 coming in the fourth quarter, the most by an individual in a fourth quarter in the NBA this season. He scored 17 points in the first half, and didn’t have a single point in the third quarter. “I give a lot of credit to our bigs,” Russell said, per The Associated Press. “They set screens and got me open, got me downhill. Once you get downhill, any player that can get downhill and see the floor like that and see the rim wide open, the sky’s the limit.“Once you get in that groove it’s hard to get you out of it. No matter what defense a team throws at you, you’re going to find a way to get it done. That’s kind of what it was.” The Nets entered the fourth quarter trailing by 25. According to ESPN, they became just the fourth team since the shot-clock era started in 1954-55 to overcome a 25-point fourth-quarter deficit.“We were at our wit’s end, it was kind of desperation,” Brooklyn coach Kenny Atkinson. “It was a little bit like, ‘Let’s conserve our main guys and kind of play it out.’ I wasn’t expecting an amazing comeback, I just have to be honest. And then slowly but surely we started cutting the lead.”The victory gave the Nets a 37-36 record as they sit seventh in the Eastern Conference, 1 1/2 games ahead of the eighth-place Heat.