Population Pharmacokinetics of Theophylline. II. Intravenous Infusion to Patients with Stable Chronic Airway Obstruction.

Abstract

The population pharmacokinetics of theophylline were studied in 55 patients with stable chronic airway obstruction. Two hundred and seventy six theophylline serum concentrations after intravenous short infusion were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, smoking habit, age and the measurement of arterial blood gases (oxygen tension: PaO2, carbon dioxide tension: PaCO2, blood pH) and clinical laboratory tests (serum albumin concentration, haematocrit) on the pharmacokinetic parameters of theophylline was examined by the likelihood ratio test. Assessment of each factor was made by a forward selection method. In the final regression model, the total body clearance (CL, l/h/kg) was related to the value of PaCO2 as well as to the presence of hepatic dysfunction, and the volume of distribution (Vd, l/kg) was related with the PaCO2 value as expressed in the following equations: CL = exp(-3.78 - 0.525.HF + 0.0233.PaCO2) and Vd = exp(-1.12 + 0.00934.PaCO2), where HF is a categorical variable with a value of unity if a patient has hepatic dysfunction otherwise zero. The interactions among blood gas measurements were observed and the CL and Vd of theophylline would be inversely correlated with PaO2 or pH, if we selected PaO2 or blood pH to be a more important factor than PaCO2. The inter-individual variabilities in CL and Vd were 38.5% and 12.5%, respectively, and the residual variability in theophylline serum concentrations was 10.6% as a coefficient of variation. This final model and the population parameters of theophylline will be useful for individualization of a drug dosage regimen by means of the Bayesian method.(ABSTRACT TRUNCATED AT 250 WORDS)

Theophylline: a review of population pharmacokinetic analyses

“…In adults, Vd was reported to also be associated with arterial blood carbon dioxide tension (PaCO 2 ). 25 The median values of Vd in paediatric patients (0Á897 L/kg) were larger than those in children (0Á57 L/kg) and in adults (0Á485 L/kg). This difference may be due to the larger volume of extracellular fluids in newborns and the increased total body water in neonates.…”

“…Among these, five articles were excluded because they were not written in English, not performed on humans, used duplicate data or were not able to provide sufficient information. Finally, a total of 16 articles [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] were selected for this review.…”

“…In paediatric patients, Vd was influenced only by body weight. In adults, Vd was reported to also be associated with arterial blood carbon dioxide tension (PaCO 2 ) . The median values of Vd in paediatric patients (0·897 L/kg) were larger than those in children (0·57 L/kg) and in adults (0·485 L/kg).…”

Population Pharmacokinetics and Pharmacodynamics of Cisplatin in Patients with Cancer: Analysis with the NONMEM Program

“…At this step, P < 0.005 was used to evaluate multiple comparisons. 13 The statistical model with proportional error was selected because a better fit was obtained than with additive error. The appropriate basic structure pharmacodynamic model and influence of patient characteristics were examined by means of the value of OBJ and likelihood ratio test described above.…”

Population pharmacokinetics of tacrolimus in adult recipients receiving living-donor liver transplantation

“…The eects of POD, serum concentrations of total bilirubin (TBIL, mg dl ±1 ), and creatinine (SCR, mg dl ±1 ), gender (GEN), and age (AGE, years) on pharmacokinetic parameters were examined using a forward-selection method [11]. That is, starting from the simplest model without any covariates, a statistically signi®cant factor was added stepwise to the descriptions of CL, V, and F. A dierence of 7.88 in the value of objective function with freedom 1 was used as statistical signi®cance (P<0.005) since multiple regression testing was performed in this analysis.…”