plasma theophylline
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PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262336
Author(s):  
Jennifer M. Reinhart ◽  
Gabriela A. R. de Oliveira ◽  
Lauren Forsythe ◽  
Zhong Li

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 μg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 μg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2473 ◽  
Author(s):  
Hsien-Tsung Yao ◽  
Jia-Hsuan Lin ◽  
Yun-Ta Liu ◽  
Mei-Ling Li ◽  
Wenchang Chiang

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline (+28.4%), dextromethorphan (+48.7%), and diltiazem (+46.7%) when co-administered an oral drug cocktail. After 7 days of feeding with an ABO-containing diet, plasma concentrations of theophylline (+45.4%) and chlorzoxazone (+53.6%) were increased after the oral administration of the drug cocktail. The major CYP enzyme activities in the liver and intestinal tract were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food–drug interactions between ABO and co-administered drugs.


2017 ◽  
pp. 263-271 ◽  
Author(s):  
M. AL ZA’ABI ◽  
A. SHALABY ◽  
P. MANOJ ◽  
B. H. ALI

Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenine-induced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver.


1996 ◽  
Vol 24 (4) ◽  
pp. 331-339 ◽  
Author(s):  
G Tatsis ◽  
G Tsoukalas ◽  
A Haviaras ◽  
A Peristerakis ◽  
V Filaditaki ◽  
...  

The bioavailability of a new sustained-release anhydrous theophylline product (Theophylline Lavipharm®) was evaluated and compared with the bioavailability of a well-established product, Theodur®. Two groups of 12 healthy non-smokers were given single doses of 200 or 300 mg of each product and two groups of 12 patients with asthma or chronic obstructive lung disease were given doses of 200 or 300 mg of each product every 12 h for 5-day periods. The values of the area under the plasma theophylline concentration against time curve (AUC), the maximum plasma theophylline concentration ( Cmax) and the time taken to reach Cmax (Tmax) for the two products did not differ significantly in the healthy groups or in the patients. The minimum and the average plasma theophylline concentrations and the fluctuation index were also calculated for the patients and there were no significant differences between the values for the two products. The new anhydrous theophylline product, Theophylline Lavipharm®, appears to show very similar bioavailability to Theodur®. No adverse reactions to the new product were reported.


1996 ◽  
Vol 22 (4) ◽  
pp. 330-341
Author(s):  
JUNKO KIZU ◽  
SHIGEKAZU WATANABE ◽  
HIDEKI ONO ◽  
JUN INATOMI ◽  
KYOKO SASAKI ◽  
...  

1994 ◽  
Vol 19 (1) ◽  
pp. 37-39
Author(s):  
O. Elidemir ◽  
S. Kó§ay ◽  
O. Hepözden ◽  
T. Aysan ◽  
M. Tufan

1992 ◽  
Vol 30 (25) ◽  
pp. 99-100

Theophylline preparations are difficult to use. Ideally doses should be adjusted to give a plasma theophylline concentration in the therapeutic range.1 This goal can be achieved when the drug is prescribed by a doctor and plasma levels are regularly measured.2 Problems could arise when these drugs are bought over the counter. This article discusses how difficulties can be avoided.


1992 ◽  
Vol 29 (4) ◽  
pp. 235-243 ◽  
Author(s):  
H. Arakawa ◽  
A. Morikawa ◽  
M. Shigeta ◽  
M. Kato ◽  
T. Kuroume ◽  
...  

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