Aminophylline clinical studies

An experimental study into the mechanism of action of enoximone in 14 patients with ischaemic or idiopathic dilative cardiomyopathy found that pretreatment with intravenous aminophylline 7 mg/kg given over 15 minutes reduced the beneficial haemodynamic eflects of intravenous enoximone 1 mg/kg given over 15 minutes. This appears to occur because each drug competes for inhibition of cAMP specific phosphodiesterases in cardiac and vascular smooth muscle. Milrinone, another phosphodiesterase inhibitor similar to enoximone, would be expected to interact in the same way. However, there are, at present, no published reports of a possible interaction with milrinone, and no case reports of a problem occurring with the concurrent use of either drug with theophylline. The clinical importance of this study therefore awaits evaluation. 

An isolated report describes an elderly woman treated with aminophylline by intravenous infusion who had a marked fall in her serum theophylline levels (from 16.3 to 6.3 mg/L) when the amino acid concentration of her parenteral nutrition regimen was increased from 4.25 to 7%. " A study in 7 patients with malnutrition (marasmus-kwashiorkor) found only a small, probably clinically irrelevant increase in the elimination of a single intravenous dose of theophylline when they were fed intravenously. ... 

A study was initiated because it was suspected that griseofulvin might possibly interact with theophylline. In 12 healthy subjects griseofulvin 500 mg daily for 8 days reduced the half-life of theophylline from 6.6 to 5.7 hours, and increased the clearance of two of its metabolites, after a single oral dose of aminophylline (Teojylamiri). However, these changes are far too small to usually have any clinical relevance. There would appear to be no reason for avoiding concurrent use. 

In contrast, a further study in healthy subjects found no clinically important interaction between intravenous aminophylline and an intravenous cimetidine infusion, but the aminophylline was given only 12 hours after starting the cimetidine, which may be insufficient for eimetidine to have had an effect. Similarly, a more recent study in 18 critically ill patients given a continuous 50-mg/hour intravenous infusion of cimetidine and low-dose aminophylline 10.8 mg/hour for just 48 hours found no clinically important interaction. ... 

Many studies in healthy subjects (given intravenous aminophylline or oral theophylline) " and patients (given sustained-release theophylline) " " have failed to find that ranitidine affects the pharmacokinetics of theophylline, even in daily doses far in excess of those used clinically (up to 4.2 g of ranitidine daily). However, there are 7 reports describing a total of 10 patients, who developed theophylline toxicity when given ranitidine with sustained-release theophylline" or intravenous aminophylline. The validity of a number of these reports has been questioned, with the authors subsequently modifying some. ... 

No clinically significant changes in serum theophylline levels were seen in 5 studies in patients (both adults and children) " or healthy subjects given josamycin, but a modest rise in theophylline levels was described in one study in children. Another study reported a23% reduction in the levels of theophylline (given as intravenous aminophylline) in 5 patients with particularly severe respiratory impairment, but no significant effect in 5 other patients with less severe disease. However, an isolated report describes theophylline toxicity in a 80-year-old man who was given josamycin. 

Similarly, no significant changes in serum theophylline levels were seen in 20 patients taking slow-release theophylline (Theo-dur) 300 mg twice daily, or intravenous theophylline 4 mg/kg three times daily, when they were given midecamycin diacetate (mioeamyein ponsinomycin) 1.2 g daily for 10 days. A number of other studies eonfirm the absence of a clinically important interaction between oral or intravenous theophylline or intravenous aminophylline and mideeamyein diaeetate in children and adults.25-28... 

In 8 healthy subjects a single 150-mg oral dose of phenylpropanolamine decreased the clearance of theophylline (given as a single 4-mg/kg intravenous dose of aminophylline 1 hour after the phenylpropanolamine) by 50%. Such a large reduction in clearance would be expeeted to result in some increase in serum theophylline levels, but so far no studies of this potentially clinically important interaction seem to have been earried out in patients. Be alert for evidence of toxicity if both drugs are used. More study is needed. See also Pseudoephedrine and related drugs + Caffeine , p.1276. 

A study of a new preparation, Phyllocon-tin tablets, consisting of aminophylline 225 mg in a continuous release base given once or twice a day to patients with asthma and/or chronic bronchitis with airways obstruction was carried out on 15 adults and 2 children aged 8 years. Clinical signs and symptoms were monitored objectively and peak expiration flow (PEP) was measured at regular weekly intervals during the treatment period of 8 weeks (7 ). All patients at the... 

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