Pharmacokinetics of theophylline in patients following short-term intravenous infusion

Abstract

Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in he therapeutic range of 8.20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean an 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl = 0.044 (0.018-0.190) l/h/kg ideal body weight, Vd = 0.451 (0.258-0.789) l/kg ideal body weight, and t 1/2(el) = 7.1 (2.6-19.1) h.

Investigating the Role of Altered Systemic Albumin Concentration on the Disposition of Theophylline in Adult and Pediatric Patients with Asthma by Using the Physiologically Based Pharmacokinetic Approach

“…The developed model has successfully predicted theophylline CL in adult patients with asthma after administering intravenous doses of 5.6 mg/kg and 351 mg, as the observed theophylline CL was 0.04 l/h per kilogram and 2.41 l/h, whereas the predicted CL was 0.05 l/h per kilogram and 3.21 l/h, respectively (Mitenko and Ogilvie, 1973; Comparison of observed and predicted systemic theophylline concentration vs. time profile in asthma population after intravenous and oral dosing. Adults with asthma after intravenous and oral application: (A) 5.6 mg/kg intravenous (Mitenko and Ogilvie, 1973), (B) 351 mg intravenous (Steinijans et al, 1982), (C) 600 mg oral (Richer et al, 1982), (D) 7.5 mg/kg oral (Weinberger and Hendeles, 1986). Children with asthma after intravenous and oral dosing: (E) 3.2 mg/kg intravenous (Loughnan et al, 1976), (F) 4 mg/kg intravenous (Ellis et al, 1976), (G) 8.2 mg/kg oral (Hendeles and Weinberger, 1985).…”

“…Theophylline-Asthma PBPK Model in Adults and Pediatrics 575 at ASPET Journals on July 18, 2021 dmd.aspetjournals.org Downloaded from Steinijans et al, 1982). Similarly, the predicted theophylline CL/F after administering oral doses of 600 mg and 7.5 mg/kg was 2.70 l/h and 0.04 l/h per kilogram, which was comparable to the observed values of 2.93 l/h and 0.04 l/h per kilogram (Richer et al, 1982;Weinberger and Hendeles, 1986).…”

“…The clinical PK data used for model evaluation were based on reported mean systemic concentration versus time profiles (Chrzanowski et al, 1977;Ishizaki et al, 1979;Antal et al, 1981;Rovei et al, 1982;Gonzalez and Golub, 1983;Gundert-Remy et al, 1983;St-Pierre et al, 1985;Lelo et al, 1986) except in one study where individual systemic concentration versus time profile was used for comparison (Lagas and Jonkman, 1983). Four studies were selected in patients with asthma with four mean PK profiles (intravenous, two; oral, two) in 134 adults with asthma (Mitenko and Ogilvie, 1973;Richer et al, 1982;Steinijans et al, 1982;Weinberger and Hendeles, 1986). Characteristics of data used for theophylline model development in adult asthma population are given in Supplemental Table 3.…”

“…The developed asthma model has efficiently predicted systemic theophylline concentrations after administration of both intravenous (5.6 mg/kg and 351 mg) and oral (7.5 mg/kg and 600 mg) doses in patients with asthma (Fig. 2, A-D) (Mitenko and Ogilvie, 1973;Richer et al, 1982;Steinijans et al, 1982;Weinberger and Hendeles, 1986). The VPCs (Fig.…”

“…2.Comparison of observed and predicted systemic theophylline concentration vs. time profile in asthma population after intravenous and oral dosing. Adults with asthma after intravenous and oral application: (A) 5.6 mg/kg intravenous(Mitenko and Ogilvie, 1973), (B) 351 mg intravenous(Steinijans et al, 1982), (C) 600 mg oral(Richer et al, 1982), (D) 7.5 mg/kg oral(Weinberger and Hendeles, 1986). Children with asthma after intravenous and oral dosing: (E) 3.2 mg/kg intravenous(Loughnan et al, 1976), (F) 4 mg/kg intravenous(Ellis et al, 1976), (G) 8.2 mg/kg oral(Hendeles and Weinberger, 1985).…”