Comparative Pharmacokinetics of Theophylline in Rabbits and in Humans with Hyperlipidemia |
| |
| Institution: | 1. Department of Pharmacy, Zhejiang Chinese Medical University, # 548 Binwen Rd., Hangzhou 310053, China;2. Department of Pharmacology, Zhejiang University School of Medicine, # 866 Yuhangtang Rd., Hangzhou 310058, China;3. Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China;1. Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran;2. Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, USA;3. Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA, USA;1. Laboratory of Physiology and Pharmacology of the Central Nervous System, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil;2. Laboratory of Pharmacology and Metabolism, Department of Pharmacology, Federal University of Paraná, Centro Politécnico, 81540-990 Curitiba, PR, Brazil |
| |
| Abstract: | The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose. Blood was sampled after 5, 10, 15, 30 and 45 min and 1, 2, 4, 6, 8, 12 and 24 h following theophylline administration. FPIA method was used to determine blood serum concentrations of theophylline. Considerable alterations of theophylline pharmacokinetics in humans suffering from mixed form of hyperlipidemia were observed. Marked decrease in area under the concentration–time curve (AUC), diminished volume of distribution, increased total body clearance, and shortened elimination half-life were observed. On the contrary, in rabbits with alimentary induced lipid metabolism disturbancest1/2of theophylline was practically unchanged and AUC only slightly increased. In conclusion: (1) hyperlipidemia affects the pharmacokinetics of theophylline in human beings, (2) rabbit model with dietetary induced lipid metabolic disturbances is not a suitable subject for estimation of pharmacokinetics of xanthine derivatives. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
