Theophylline distribution

Lactation Theophylline distributes readily into breast milk. 

A 20-year-old man is hospitalized after an asthmatic attack precipitated by an upper respiratory infection and fails to respond in the emergency room to two subcutaneously injected doses of epinephrine. The patient has not been taking theophylline-containing medications for the past 6 weeks. He weighs 60 kg and you estimate that his apparent volume of theophylline distribution is 0.45 L/kg. Bronchodilator therapy includes a 5.6-mg/kg loading dose of aminophylline, infused intravenously over 20 min, followed by a maintenance infusion of 0.63 mg/kg per hour (0.50 mg/kg per hour of theophylline). Forty-eight hours later, the patient s respiratory status has improved. However, he has nausea and tachycardia, and his plasma theophylline level is 24 xg/mL. 

Belknap SM, Nelson JE, Ruo TI, Frederiksen MC, Worwag EM, Shin S-G, Atkinson AJ Jr. Theophylline distribution kinetics analyzed by reference to simultaneously injected urea and inulin. J Pharmacol Exp Ther 1987 243 963-9. 

TABLE 22.2 Comparison of Expected with Measured Values of Theophylline Distribution Volume s... 

Phenylpropanolamine also increases caffeine plasma levels. Whether there is also an effect on theophylline distribution kinetics is a matter of some debate (Lake et al., 1990 Upton, 1991). Even if such an effect does exist, however, it is not known whether such an effect would be of any clinical significance in the case of ma huang, which contains only very small amounts of pure phenylpropanolamine. Reduced metabolism of pseudoephedrine is... 

Mazzafera P (1994) Caffeine, theobromine and theophylline distribution in Ilex paraguariensis. Rev Brasil Fisiol Veg 6 149-151... 

Initially, it was beheved that the abiUty of xanthines phosphodiesterase (PDF) led to bronchodilation (Fig. 2). One significant flaw in this proposal is that the concentration of theophylline needed to significantly inhibit PDE in vitro is higher than the therapeutically useful semm values (72). It is possible that concentration of theophylline in airways smooth muscle occurs, but there is no support for this idea from tissue distribution studies. Furthermore, other potent PDE inhibitors such as dipyridamole [58-32-2] are not bronchodilators (73). EinaHy, although clinical studies have shown that neither po nor continuous iv theophylline has a direct effect on circulating cycHc AMP levels (74,75), one study has shown that iv theophylline significant potentiates the increase in cycHc AMP levels induced by isoproterenol (74). 

It has a water solubility of about 55%. It may ba compounded in the form of tablets, for oral administration, or may be prepared in solution for distribution in ampoules. For tha manufacture of solutions for packaging in ampoules. It is more convenient to simply dissolve tha theophylline and tha butanol amine in water, without going through the intermediate step of separating the crystalline salt. 

Distribution - Average volume of distribution is 0.45 L/kg (range, 0.3 to 0.7 L/kg). Theophylline does not distribute into fatty tissue. Approximately 40% is bound to plasma protein. Therapeutic serum levels generally range from 10 to 20 mcg/mL. 

The purine derivatives caffeine, theobromine, and theophylline (Figure 6.135) are usually referred to as purine alkaloids. As alkaloids they have a limited distribution, but their origins are very closely linked with those of the purine bases adenine and guanine, fundamental components of nucleosides, nucleotides, and the nucleic acids. Caffeine, in the form of beverages such as tea, coffee, and cola is one of the most widely consumed and socially accepted natural stimulants. It is also used medicinally, but theophylline is... 

The SIMS image of the 0 ions for the sectioned polymer coated theophylline beads is shown in Figure 9. The distribution of the 0 ions is primarily concentrated in the region of the polymeric membrane coating and highlights the continuity of the polymeric film. 

To follow the analysis, it is particularly important to understand the mechanism implied by the null hypothesis. Figure 6.2 will be used to describe these alleged events. A vertical scale shows theophylline clearances. Each circle (open or solid) represents a member of the population. The data form normal distributions (but these are shown turned at right angles to the usual orientation). 

Stahle L (1991) Drug distribution studies with microdialysis I. Tissue dependent difference in recovery between caffeine and theophylline. Life Sci 49 1835-1842. 

NIFEDIPINE THEOPHYLLINE Clinically non significant 1 theophylline levels with nifedipine, but there are case reports of theophylline toxicity after starting nifedipine Uncertain probably due to alterations in either metabolism or volume of distribution of theophylline Be aware of the small possibility of theophylline toxicity when commencing calcium channel blockers check levels if any problems occur, and consider either reducing the dose of theophylline or using an alternative calcium channel blocker... 

Volume of Distribution. Theophylline-7-acetic acid 0.5 litre/ kg (single subject). 

Disposition in the Body. Readily absorbed after oral administration of aminophylline less rapidly absorbed when given as theophylline irregularly absorbed after rectal administration. Rapidly and widely distributed throughout the tissues. Metabolised by V-demethylation to form 3-methylxanthine (which is active but less potent than theophylline), 1,3-dimethyluric acid, and 1-methyluric acid. In adults, about 13% of a dose is excreted in the urine in 24 hours as unchanged drug, with about 15% as... 

Sedek GS, Ruo TI, Frederiksen MC, Frederiksen JW, Shih S-R, Atkinson AJ Jr. Splanchnic tissues are a major part of the rapid distribution spaces of inulin, urea and theophylline. J Pharmacol Exp Ther 1989 251 963-9. 

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