{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:58:06Z","timestamp":1780052286362,"version":"3.53.1"},"reference-count":23,"publisher":"S. Karger AG","issue":"5","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2010]]},"abstract":"<i>Aims:<\/i> Pentoxifylline and lisofylline are methylxanthine derivatives that exhibit anti-inflammatory activity both in vitroand in vivo. This study was designed to develop a pharmacokinetic-pharmacodynamic (PK\/PD) model to describe the inhibitory effect of these compounds on TNF-\u03b1 production in mice challenged with bacterial lipopolysaccharide (LPS). <i>Methods:<\/i> Male CD-1 mice received increasing intravenous doses of either compound simultaneously with high-dose LPS. A 2-compartment model with Michaelis-Menten-type elimination was used to describe the drug concentration versus time data. Serum TNF-\u03b1 levels were fitted to an indirect response model. <i>Results:<\/i> Pentoxifylline and lisofylline reduced LPS-induced TNF-\u03b1 serum concentrations in a dose-dependent manner. PK\/PD analysis revealed an almost 2-fold higher estimate of K<sub>m<\/sub> for pentoxifylline in comparison to lisofylline. The production and elimination rates of TNF-\u03b1 were: k<sub>in<\/sub> = 2,167 pg\/ml \u00b7 h<sup>\u20131<\/sup> and k<sub>out<\/sub> = 1.65 h<sup>\u20131<\/sup>, respectively. The drug concentration causing 50% of TNF inhibition (IC<sub>50<\/sub>) was markedly lower for pentoxifylline (0.47 vs. 1.61 \u00b5g\/ml). <i>Conclusions:<\/i>It seems that pentoxifylline is more potent than lisofylline in inhibiting TNF-\u03b1 production in vivo. The proposed PK\/PD model allowed a better understanding of the pharmacological properties of both methylxanthine derivatives and may be helpful in appropriate dosage selection for further studies.<\/jats:p>","DOI":"10.1159\/000288734","type":"journal-article","created":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T07:11:01Z","timestamp":1270710661000},"page":"264-271","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacokinetic-Pharmacodynamic Modeling of Methylxanthine Derivatives in Mice Challenged with High-Dose Lipopolysaccharide"],"prefix":"10.1159","volume":"85","author":[{"given":"Elzbieta","family":"Wyska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2010,4,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.bcp.2004.08.012"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.bmt.1702114"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.91.9.3857"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2FS1043-6618%2803%2900002-1"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.2165%2F00003088-200342120-00001"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1365-3083.1986.tb02194.x"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016%2FS0140-6736%2887%2991728-4"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1097%2F00003246-199711000-00018"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1046%2Fj.1365-2567.1997.00252.x"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1097%2F00003246-199602000-00005"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1097%2F00003246-199904000-00042"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1002%2Fchir.20299"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002%2Fjps.20257"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1007%2FBF01972721"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2FS0009-9236%2899%2970110-4"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038%2Fnrd1854"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1021%2Fjs970382f"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002%2Fchir.10121"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1211%2Fjpp.59.4.0003"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.intimp.2009.01.013"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007%2FBF02353461"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1007%2FBF01059667"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.2133%2Fdmpk.24.16"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/288734","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/288734","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T19:50:42Z","timestamp":1745437842000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000288734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010]]},"references-count":23,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2010,5,1]]},"published-print":{"date-parts":[[2010,5,28]]}},"URL":"https:\/\/doi.org\/10.1159\/000288734","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010]]}}}