[Evaluation of theophylline population pharmacokinetics in adult hospitalized patients using NONMEM analysis].
The population pharmacokinetics of theophylline was evaluated using 374 theophylline serum concentration measurements from 72 hospitalized patients through NONMEM analysis. An one-compartment open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on Cl and Vd were investigated. Hypothesis testing to evaluated potentially significant factors produced a final regression model. There were about 1.25% per year decrease in Cl at the age of 18-77. Cl was reduced by 26.8% for patients with long history of theophylline administration and multiple dosings, and reduced by 33.9% in OLD patients. Sex, body weight, and coadministration of acetylspiramycin had no significant effects on Cl. Vd was proportional to body weight. The final regression model allowed a priori estimate of the theophylline pharmacokinetic parameters in the patients. These results may be helpful to a rational individualized theophylline dosage regimen.
Department of Clinical Pharmacology, Jingling Hospital, Nanjing, China.
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D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012044:Regression Analysis; D015572:Spiramycin / Q000008:administration & dosage / Q000031:analogs & derivatives; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*
C033163:acetylspiramycin; D015572:Spiramycin; D013806:Theophylline