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• W2044480037 abstract "1. The in vitro biological activities and the effect of protein binding on the relaxant effects in vivo of N-3-alkylxanthine and N-3-alkyl-N-1-methylxanthine derivative were investigated in guinea-pigs. 2. A significantly positive correlation was observed among the in vitro muscle relaxant activity, the cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) inhibitory activity and the protein-binding potency of xanthine derivatives. However, there was a weak relationship between these activities and affinity for adenosine receptors. 3. When theophylline, enprofylline and 1-methyl-3-propylxanthine (MPX) were injected intravenously in guinea-pigs, their ED50 values were 6.1, 3.3 and 1.0 mg/kg, respectively. Plasma concentrations of these drugs obtained following the intravenous injection of the ED50 approximated the theoretically effective concentration (EC50) predicted from both the relaxant effects in vitro and the protein binding parameters. A good linear correlation was observed between bodyweight in four species (rats, guinea-pigs, rabbits and humans) and certain pharmacokinetic parameters of enprofylline and theophylline. 4. The present study indicates that differences in the relaxant effects of these drugs in vitro and in vivo can be explained in part by protein binding, and that the protein binding of these xanthine bronchodilators is an important determinant for their pharmacological activity. Guinea-pigs provide a useful model for studying pharmacodynamic-pharmacokinetic relationships of new bronchodilators." @default.
• W2044480037 created "2016-06-24" @default.
• W2044480037 creator A5001620097 @default.
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• W2044480037 date "1992-06-01" @default.
• W2044480037 modified "2023-10-18" @default.
• W2044480037 title "BRONCHODILATORY ACTIVITY AND PHARMACOKINETICS OF NEW XANTHINES IN GUINEA-PIGS" @default.
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• W2044480037 doi "https://doi.org/10.1111/j.1440-1681.1992.tb00488.x" @default.
• W2044480037 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1318809" @default.
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