The effect of assay methods on plasma levels and pharmacokinetics of theophylline: HPLC and EIA.

Ishizaki, Takashi; Watanabe, Misa; Morishita, Nobumichi

doi:10.1111/j.1365-2125.1979.tb00942.x

Cited by 14 publications

(6 citation statements)

References 35 publications

(53 reference statements)

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“…HPLC was used to determine the concentration of insulin [10], vancomycin [11] or theophylline [12] in each sample. The HPLC conditions used for each drug are described in Table 1.…”

Section: In Vitro Release Studiesmentioning

confidence: 99%

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

Morishita

Lowman

Takayama

et al. 2002

Journal of Controlled Release

151

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The objective of this study was to investigate the insulin incorporation and release properties of poly(methacrylic acid-g-ethylene glycol) P(MAA-g-EG) microparticles as a function of copolymer composition. These microparticles exhibited unique pH-responsive characteristics in which interpolymer complexes were formed in acidic media and dissociated in neutral / basic environments. The microparticles containing equimolar amounts of MAA and PEG were capable of efficient insulin loading using equilibrium partitioning (>90%). Additionally, insulin release from the gel was significantly retarded in acidic media while rapid release occurred under neutral / basic conditions. In contrast, as the amount of MAA of the polymer was increased, the entrapment efficiency of insulin within the gel greatly reduced and the insulin was readily released from the polymer network in the acidic and neutral / basic media. In addition, in order to evaluate the potential application of the microparticles to other drugs, theophylline, vancomycin, fluoresceinisothiocyanate-labeled dextrans (FITC-Ds) with average molecular weights of 4400 (FITC-D-4), 12,000 (FITC-D-10) and 19,500 were utilized as model hydrophilic drugs. The incorporation profiles showed that the uptake of theophylline and vancomycin to the microparticles was lower than that of insulin. Additionally, polymer microparticles loaded with theophylline and vancomycin exhibited pH-sensitive release behavior, however, the oscillatory behavior is less pronounced than those of insulin. The values of drug incorporation ratio showed that the microparticles were capable of incorporating almost 90% of insulin and 15% of vancomycin from solution. On the other hand, the other hydrophilic drugs showed very low incorporation efficiency to the microparticles. These data suggest that gels containing equimolar amounts of MAA:EG have the potential to be used as an oral carrier of peptide drugs, especially for insulin.

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“…HPLC was used to determine the concentration of insulin [10], vancomycin [11] or theophylline [12] in each sample. The HPLC conditions used for each drug are described in Table 1.…”

Section: In Vitro Release Studiesmentioning

confidence: 99%

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

Morishita

Lowman

Takayama

et al. 2002

Journal of Controlled Release

151

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“…The observed and predicted systemic theophylline concentration versus time profiles after administering different intravenous doses (4-6 mg/kg and 193.2-386.4 mg) in the healthy population are shown in Fig. 1, A-F (Chrzanowski et al, 1977;Ishizaki et al, 1979;Gundert-Remy et al, 1983;St-Pierre et al, 1985). It is apparent from the VPCs that the model has successfully apprehended the observed PK data after intravenous application.…”

Section: Healthy Adult Populationmentioning

confidence: 88%

“…The PBPK model development process was initiated by selecting drug specific parameters that govern theophylline disposition Comparison of observed and predicted systemic theophylline concentration vs. time profile in healthy subjects after intravenous and oral dosing. Healthy population after intravenous application: (A) 4 mg/kg (Ishizaki et al, 1979), (B) 2.78 mg/kg (Ishizaki et al, 1979), (C) 3.84 mg/kg (Chrzanowski et al, 1977), (D) 193.2 mg (Gundert-Remy et al, 1983), (E) 386.4 mg (Gundert-Remy et al, 1983), (F) 6 mg/kg (St-Pierre et al, 1985) and after oral application: (G-J) 125-500 mg (Rovei et al, 1982), (K and L) 200 mg geriatric and adult (Antal et al, 1981), (M) 250 mg (Lelo et al, 1986), (N and O) 600 mg sprinkle (N) and tablet (O) (Gonzalez and Golub, 1983), and (P) 250 mg (Lagas and Jonkman, 1983). The observed data are shown as solid red circles.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, nine pharmacokinetic studies were selected for model development and evaluation in healthy adults. These studies include 17 systemic concentration versus time profiles (intravenous, 6; oral, 11) in 114 healthy individuals (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;Lagas and Jonkman, 1983;St-Pierre et al, 1985;Lelo et al, 1986). Characteristics of healthy population data used for theophylline model development are given in Supplemental Table 2.…”

Section: Clinical/pharmacokinetic Datamentioning

confidence: 99%

“…Characteristics of healthy population data used for theophylline model development are given in Supplemental Table 2. 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).…”

Section: Clinical/pharmacokinetic Datamentioning

confidence: 99%

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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

et al. 2020

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Theophylline is commonly used for the treatment of asthma and has a low hepatic clearance. The changes in plasma albumin concentration occurring in asthma may affect the exposure of theophylline. The aim of the presented work was to predict theophylline pharmacokinetics (PK) after incorporating the changes in plasma albumin concentration occurring in patients with asthma into a physiologically based pharmacokinetic (PBPK) model to see whether these changes can affect the systemic theophylline concentrations in asthma. The PBPK model was developed following a systematic model building approach using Simcyp. The predictions were performed initially in healthy adults after intravenous and oral drug administration. Only when the developed adult PBPK model had adequately predicted theophylline PK in healthy adults, the changes in plasma albumin concentrations were incorporated into the model for predicting drug exposure in patients with asthma. After evaluation of the developed model in the adult population, it was scaled to children on physiologic basis. The model evaluation was performed by using visual predictive checks and comparison of ratio of observed and predicted (R obs/Pre ) PK parameters along with their 2-fold error range.The developed PBPK model has effectively described theophylline PK in both healthy and diseased populations, as R obs/Pre for all the PK parameters were within the 2-fold error limit. The predictions in patients with asthma showed that there were no significant changes in PK parameters after incorporating the changes in serum albumin concentration. The mechanistic nature of the developed asthma-PBPK model can facilitate its extension to other drugs. SIGNIFICANCE STATEMENTExposure of a low hepatic clearance drug like theophylline may be susceptible to plasma albumin concentration changes that occur in asthma. These changes in systemic albumin concentrations can be incorporated into a physiologically based pharmacokinetic model to predict theophylline pharmacokinetics in adult and pediatric asthma populations. The presented work is focused on predicting theophylline absorption, distribution, metabolism, and elimination in adult and pediatric asthma populations after incorporating reported changes in serum albumin concentrations to see their impact on the systemic theophylline concentrations.

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Analytical reliability of methods to determine theophylline in serum or plasma

Börner

Staib

Schuppan

et al. 1980

Methods in Clinical Pharmacology

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The effect of assay methods on plasma levels and pharmacokinetics of theophylline: HPLC and EIA.

Cited by 14 publications

References 35 publications

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers

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

Analytical reliability of methods to determine theophylline in serum or plasma

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