2008
DOI: 10.1080/00498250801935974
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Pharmacokinetics and metabolism of KW-4490, a selective phosphodiesterase 4 inhibitor: Difference in excretion of KW-4490 and acylglucuronide metabolites between rats and cynomolgus monkeys

Abstract: 1. The pharmacokinetics and metabolism of KW-4490, a selective phosphodiesterase 4 inhibitor, were investigated in rats and monkeys. After oral administration, KW-4490 was rapidly absorbed, and then its plasma concentrations apparently declined with half-lives of approximately 5 h in rats and 3.5 h in cynomolgus monkeys; however, a number of secondary peaks were apparent in the profiles for both species. The plasma pharmacokinetics of KW-4490 were comparable between rats and monkeys. 2. After oral administrati… Show more

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“…In another separate report that described the development and application of a sensitive tandem mass spectrometric method for bupropion and hydroxybupropion, double or secondary peaks were observed to manifest for the major metabolite hydroxybupropion, although such peaks were not observed for bupropion, the parent compound (Parekha et al, 2011). The occurrence of such double or secondary peaks in plasma profiles are not a recent phenomenonit has been reported for a number of compounds both in preclinical and clinical studies (Chi et al, 2011;Guo et al, 2011;Xiao et al, 2010;Sawant et al, 2010;Hendrickson et al, 2010;Lehr et al, 2009;Sidharta et al, 2009;Metsugi et al, 2008;Fujita et al, 2008;Huang et al, 2007;Alousi et al, 2007;Okusanya et al, 2007;Ma et al, 2006;Piyapolrungroj et al, 2000;Ogiso et al, 2001;Wang et al, 1999;Plusquellec et al, 1998;Lipka et al, 1995). The intention of this communication is to provide some considerations and perspectives on the double or multiple/secondary peak phenomenon with applicable bioanalytical strategy.…”
mentioning
confidence: 89%
“…In another separate report that described the development and application of a sensitive tandem mass spectrometric method for bupropion and hydroxybupropion, double or secondary peaks were observed to manifest for the major metabolite hydroxybupropion, although such peaks were not observed for bupropion, the parent compound (Parekha et al, 2011). The occurrence of such double or secondary peaks in plasma profiles are not a recent phenomenonit has been reported for a number of compounds both in preclinical and clinical studies (Chi et al, 2011;Guo et al, 2011;Xiao et al, 2010;Sawant et al, 2010;Hendrickson et al, 2010;Lehr et al, 2009;Sidharta et al, 2009;Metsugi et al, 2008;Fujita et al, 2008;Huang et al, 2007;Alousi et al, 2007;Okusanya et al, 2007;Ma et al, 2006;Piyapolrungroj et al, 2000;Ogiso et al, 2001;Wang et al, 1999;Plusquellec et al, 1998;Lipka et al, 1995). The intention of this communication is to provide some considerations and perspectives on the double or multiple/secondary peak phenomenon with applicable bioanalytical strategy.…”
mentioning
confidence: 89%