Dose-Dependent Theophylline Elimination in an Adult

1983 ◽  
Vol 17 (3) ◽  
pp. 202-204 ◽  
Author(s):  
Richard J. Creger ◽  
William D. Ball ◽  
Michael F. Bahntge

A 69-year-old male patient with chronic obstructive pulmonary disease exhibited dose-dependent theophylline elimination. Steady-state serum theophylline concentrations, obtained at five different aminophylline infusion rates, ranged from 2.0 mg/L at an infusion rate of 36 mg/h to 10.1 mg/L at 76 mg/h. These serum concentrations were nonlinearly related to dose, with a Vmax of 89.04 mg/h and Km of 3.96 mg/L (r = 0.983, p < 0.005). Theophylline clearance fell from a high of 348 ml/kg/h to 145 ml/kg/h as the infusion rate was increased. Although theophylline elimination kinetics in adults are generally assumed to be linear, clinicians should be alert to the possibility of nonlinear theophylline elimination, as has been observed commonly in children.

1995 ◽  
Vol 29 (4) ◽  
pp. 378-380 ◽  
Author(s):  
Paul R Matuschka ◽  
Richard S Vissing

Objective: To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD). Case Summary: A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 µmol/L (normal 55—110). A subsequent concentration was subtherapeutic (46.62 µmol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv ql2h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 µmol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range. Discussion: The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxo-quinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations. Conclusions: The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.


Kardiologiia ◽  
2020 ◽  
Vol 60 (7) ◽  
pp. 44-52
Author(s):  
L. A. Shpagina ◽  
N. V. Kamneva ◽  
L. M. Kudelya ◽  
O. S. Kotova ◽  
I. S. Shpagin ◽  
...  

Aim      Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are a common comorbidity. Professional chronic obstructive pulmonary disease (PCOPD) is a specific phenotype, which suggests peculiarities in the development of HF. Difficulties of HF diagnosis in such patients determine the relevance of searching for additional markers. The aim of the study was identifying HF markers in patients with PCOPD.Material and methods  This single-site, cohort, prospective, observational study included 345 patients. The main group consisted of PCOPD patients; the comparison group consisted of patients with COPD induced by tobacco smoking; and the control group included conventionally healthy individuals. The groups were matched by the index of coincidence; pairs were matched at 1:1 by the “nearest neighbor index”; covariates for matching included COPD duration, sex, and age. Each group included 115 patients. The major professional adverse factors were silica-containing dust and organic solvents. COPD was diagnosed according to GOLD criteria; HF was diagnosed in accordance with Russian clinical guidelines. The markers were determined by multifactorial logistic regression. Likelihood of events with allowance for the time to the event was analyzed by the Kaplan-Meier method.Results HF in PCOPD patients was characterized by biventricular damage, preserved left ventricular ejection fraction, and frequent hospitalizations for decompensation (17.5 % vs. 9.5 % for COPD in smokers). HF markers in patients with PCOPD included the length of work of more than 20 years, pulmonary artery systolic pressure (PASP) higher than 35 mm Hg according to data of Doppler echocardiography, diffusing capacity of lungs for carbon monoxide (DLCO) less than 50 %, increased serum concentrations of CC-chemokine ligand 18 (CCL18), S-100‑beta protein, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Diagnostic sensitivity of the multifactorial model was 84 % and specificity was 81 %. Two models were proposed for purposes of screening, which included the following parameters: length of work, exposure to aromatic hydrocarbons, decreased distance in 6-min walk test by more than 60 m per year and length of work, exposure to inorganic dust, and decreased forced expiratory volume during the first second by more than 55 ml per year.Conclusion      The markers for development of HF in PCOPD patients are length of work >20 years, PASP >35 mm Hg, DLCO <50 %, and increased serum concentrations of CCL18, S-100‑beta protein, and NT-pro-BNP.


2002 ◽  
Vol 72 (6) ◽  
pp. 360-368 ◽  
Author(s):  
Liv Førli ◽  
Jan Pedersen ◽  
Øystein Bjørtuft ◽  
Rune Blomhoff ◽  
Johan Kofstad ◽  
...  

The objective of the study was to examine whether serum concentrations of retinol (vitamin A) and alpha-, beta-, and gamma-tocopherols (vitamin E) are affected by underweight and weight gain. The analysis was carried out in underweight (n = 42, of whom 24 had chronic obstructive pulmonary disease) and normal-weight (n = 29, of whom 16 had chronic obstructive pulmonary disease) candidates for lung transplantation before and after dietary intervention for weight gain. In all the patients, serum concentrations of retinol at baseline and changes in retinol were positively associated with body mass index (unstandardized regression coefficient, b = 0.03; p = 0.05) and an increase in weight (b = 0.09, p = 0.02) after dietary intervention, respectively. At baseline, serum retinol concentrations were positively correlated with forced vital capacity (b = 0.24, p < 0.05) and forced expiratory volume in one second (b = 0.17, p < 0.05). In patients with chronic obstructive pulmonary disease (COPD), tocopherols were higher in the underweight patients than in the normal-weight ones, while it was an opposite tendency in patients with other lung diseases. Only in patients with lung diseases other than COPD was there found a positive association between tocopherols and lung gas diffusion. In patients with other diagnoses compared with patients with COPD, a positive change in serum tocopherol status after weight gain was suggested.


1985 ◽  
Vol 7 (2) ◽  
pp. 168-173 ◽  
Author(s):  
James W. Bredon ◽  
J. Lyle Bootman ◽  
William N. Jones ◽  
William F. McGhan ◽  
Donald G. Perrier ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Biaoxue Rong ◽  
Tian Fu ◽  
Congxue Rong ◽  
Wen Liu ◽  
Kai Li ◽  
...  

Abstract This study aimed to investigate the association between serum concentrations of chemokine (C–C Motif) ligand 18 (CCL-18) and interleukin 23 (IL-23) and clinical parameters of chronic obstructive pulmonary disease (COPD). The serum concentrations of CCL-18 and IL-23 were tested by enzyme linked immunosorbent assay (ELISA). The association between their concentrations and clinical parameters of COPD patients were analyzed by linear regression, logistic regression and ROC curve. The results showed that the serum concentrations of CCL-18 and IL-23 in COPD patients were increased compared with healthy people (P < 0.001) and that patients with acute exacerbation of COPD (AECOPD) had higher serum CCL-18 and IL-23 concentrations than stable patients (P < 0.001). Synergistic increase of CCL-18 and IL-23 in COPD patients was positively correlated with COPD patients' higher GOLD grade (P < 0.001), higher mMRC score (P < 0.001) and longer medical history (P < 0.001), but negatively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (P < 0.001) and FEV1% predicted (P < 0.001). The serum concentrations of CCL-18 and IL-23 were most related to the GOLD grade (OR = 2.764 for CCL-18 and OR = 4.215 for IL-23) and detection of both showed considerable sensitivity (72.57% for CCL-18 and 76.92% for IL-23) and specificity (92.50% for CCL-18 and 77.5% for IL-23) in identifying COPD. Increased serum concentrations of CCL-18 and IL-23 correlated with the disease progression of COPD and they could be used as biomarkers for disease evaluation of COPD.


Sign in / Sign up

Export Citation Format

Share Document