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At least 19 recordsLinked to original sources

PubMed1985

Bioavailability of dyphylline and dyphylline-guaifenesin tablets in humans.

A six-way-crossover bioavailability study was conducted with twelve healthy male volunteers to evaluate the relative bioavailability of three tablet formulations containing dyphylline and three tablet formulations containing dyphylline-guaifenesin. Each subject was administered two tablets of each product with greater than or equal to 3 d separating each dose. Blood samples were obtained just prior to each dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, and 10.0 h following each dose. An HPLC method was used to assay dyphylline in the serum. The mean tmax ranged from 0.6 to 1.0 h for the six products. The mean values for Cmax differed by 29%, and the AUC values differed by less than 8%. It was noted that the dyphylline-guaifenesin products exhibited a lower bioavailability than the products which only contained dyphylline. It was concluded that the three combination products were bioequivalent, as were the three dyphylline products.

Adult↗

PubMed1988

Dyphylline prodrugs: plasma hydrolysis and dyphylline release in rabbits.

Ester hydrolysis of prodrugs of dyphylline [7-(2,3-dihydroxypropyl)theophylline] followed first-order kinetics in both human and rabbit plasma. Rate constants were estimated by linear regression analysis of initial conversion rates, determined at different initial prodrug concentrations. Release of dyphylline from different prodrugs was 1.3 to 13 times faster in rabbit plasma than human plasma. However, relative rates of drug release (lability order) followed the same patterns in rabbit and human plasma. Dyphylline concentrations in rabbit plasma were extended slightly following intravenous administration of dyphylline 2',3'-dipivaloate. Oral dosing of the prodrug in rabbits greatly sustained plasma dyphylline concentrations.

Animals↗

PubMed1992

Dyphylline liposomes for delivery to the skin.

Delivery of dyphylline to the skin using liposomes was investigated. Xanthines are inhibitors of cAMP phosphodiesterase and have been considered for treatment of psoriasis. Dyphylline was chosen because of its solubility in water, which should allow for incorporation of higher concentrations within the liposomes. Liposomes containing dyphylline were prepared by a method using sonication. Transmission electron micrography (TEM) visualization showed small particles ranging from 40 to 100 nm, and particle size distribution determined by light scattering showed the vesicles to have an average diameter of 360 nm. The transdermal delivery of free dyphylline and dyphylline incorporated in unilamellar liposomes was measured from polyethylene glycol (PEG), Carbopol gel, a PEG enhancer base, and water. For comparison, similar experiments were carried out with theophylline as well. When the drugs were incorporated in Carbopol gel, a large difference was seen between their fluxes, with free dyphylline having the highest permeation, followed by liposomal dyphylline, and then theophylline. With the PEG enhancer base, a very high permeation of theophylline was observed relative to dyphylline and liposomal dyphylline. From the PEG base, liposomal dyphylline exhibited the lowest skin permeation flux relative to other bases. Using the PEG base for dyphylline incorporated in liposomes, a high skin partitioning of the drug, along with low transdermal permeation, was measured. These results may indicate that the drug is localized in the skin.

Animals↗

PubMed1981

Dyphylline aerosol attenuates antigen-induced bronchoconstriction in experimental canine asthma.

This study compared the bronchodilator effect in experimental canine asthma of dyphylline administered by aerosol and intravenous routes in doses producing equivalent concentrations of the drug in the plasma. Pulmonary resistance (RL) was calculated from simultaneous measurements of pressure and flow during fixed-volume controlled ventilation at the same peak flow and corrected for elastic recoil pressure. Dynamic compliance (Cdyn) was calculated by dividing tidal volume by the change in pressure measured between points of zero flow. Concentrations of dyphylline in the plasma were measured using high-performance liquid chromatographic techniques. Rates of infusion of dyphylline were determined from values for clearance observed in preliminary experiments with intravenous injection. Prior to exposure to antigen, RL and Cdyn were not significantly different in control and dyphylline-treated dogs. Following challenge, with antigen RL increased by 8.3 +/- 2.6 times (mean +/- SE) in untreated dogs but only by 2.4 +/- 0.4 times in dyphylline treated dogs. Levels of dyphylline in the plasma averaged 4.2 micrograms/ml +/- 0.6 micrograms/ml at the end of the ten-minute period of aerosol administration and remained at that level for 60 minutes. At equivalent plasma levels (4.3 micrograms/ml +/- 0.3 micrograms/ml), infusion of dyphylline did not significantly after the response to Ascaris antigen, whereas dyphylline administered by the aerosol route markedly attenuated the response.

Aerosols↗

PubMed1983

Effect of probenecid on dyphylline elimination.

Dyphylline is a methylxanthine bronchodilator with such a short a biologic t 1/2 that development of practical dosing regimens has been difficult. Because its rapid renal elimination suggests active secretion, the effect of 1 gm probenecid on single-dose elimination kinetics of dyphylline was determined. Twelve subjects (six male, six female) participated in a crossover design. Subjects were their own controls and received dyphylline, 20 mg/kg orally, alone and after probenecid. The dyphylline t 1/2 increased from 2.57 +/- 0.45 to 4.88 +/- 1.2 hr, whereas the elimination rate constant decreased from 0.276 +/- 0.056 to 0.150 +/- 0.037 hr-1 after probenecid. There was no significant change in the dyphylline apparent volume of distribution. Dyphylline total body clearance fell from 173 +/- 20 to 95 +/- 12 ml/kg . hr. The combined use of these drugs may lead to a practical dyphylline dosage schedule in aminophylline-hypersensitive patients or those incapacitated by theophylline gastrointestinal side effects.

Chromatography, High Pressure Liquid↗

PubMed1981

Pharmacokinetics of dyphylline elimination by uremic patients.

The elimination kinetics of dyphylline were investigated in four uremic patients receiving chronic hemodialysis treatment. Dyphylline (1000 mg) was administered to each patient orally 2 hr before hemodialysis. Serial arterial and venous blood samples as well as outflowing dialysate samples were collected and analyzed by high-pressure liquid chromatography for dyphylline. The extraction efficiency of the hollow-fiber dialyzers averaged 44.6%. The mean dialysis clearance was 108.7 ml/min which compares favorably to the 57 ml/min metabolic clearance of the drug. A mean of 278.6 mg or 28.34% of the administered dose was recovered in the dialysate during the 4-hr dialysis interval. Half-lives for dyphylline during dialysis ranged from 3.43 to 7.62 hr. The off-dialysis half-lives for two of the four patients studied on a separate occasion were 10.6 and 13.2 hr. The overall clearance calculation projects an average half-life reduction of approximately 65% during hemodialysis. We conclude that dyphylline is dialyzable. Hemodialysis patients receiving dyphylline treatment may require a dosage regimen alteration. In addition, hemodialysis may be useful for the treatment of dyphylline overdose because of its effectiveness in accelerating the removal of the drug.

Adult↗

PubMed1979

Urinary excretion of dyphylline in humans.

The pharmacokinetics and urinary excretion of a single dyphylline dose were studied in five normal volunteers. The mean dyphylline half-life was 1.8 +/- 0.2 hr; the mean total body clearance rate and mean renal clearance rate were 333 +/- 62 and 276 +/- 52 ml/min, respectively; and the mean volume of distribution was 0.8 +/- 0.2 liter/kg. In the urine, 83 +/- 5% of the dose was excreted as unchanged drug, and theophylline was not detected. Dyphylline doses of 19--27 mg/kg, resulting in peak serum dyphylline concentrations of 19.3--23.5 micrograms/ml, were tolerated well by four subjects. One subject had a severe headache following a 28-mg/kg dose, associated with a peak serum dyphylline concentration of 36.4 micrograms/ml. This study confirms speculation that dyphylline is not metabolized to theophylline in vivo.

Adult↗

PubMed1979

Comparative pharmacokinetics of theophylline and dyphylline following intravenous injection in rabbits.

The pharmacokinetics of theophylline and dyphylline in four rabbits were investigated following intravenous injection. Each rabbit received theophylline (10 mg/kg) first then dyphylline (25 mg/kg) two weeks afterwards as an intravenous bolus injection. The serum concentration-time data for both theophylline and dyphylline were best fitted to the two compartment open model. The half-lives of theophylline and dyphylline were 5.5 +/- 1.3 and 0.74 +/- 0.10 hr, respectively. The apparent volume of distribution (Vdbeta) and total body clearance (TBC) of dyphylline (Vdbeta = 1008 +/- 156 ml/kg; TBC = 942 +/- 118 ML/HR/KG)a = 1008 +/- 156 ml/kg; TBC = 942 +/- 118 ml/hr/kg) were much higher than those of theophylline (Vdbeta = 545 +/- 160 ml/kg; TBC = 69 +/- 10 ml/hr/kg). Thus both theophylline and dyphylline showed pronounced difference in their pharmacokinetic profile.

Animals↗

PubMed1976

The effects of dyphylline [7-(2,3-dihydroxypropyl) theophylline] on the toxicity of hycanthone on the frog's heart.

The effects of the topical application of Dyphylline in concentrations of 1.0 mg/1.0 ml and 10 mg/1.0 ml Ringer's solution and 25 mg/1.0 ml, 0.065% NaCl solution (the content of ampoules in clinical use) were investigated on frog's heart in situ. Dyphylline in all of the above concentrations had a stimulatory effect on the frog's heart. Hycanthone methanesulphonate in concentration of 1.0 ml/1.0 ml when topically applied to the frog's heart had a depressant effect on both of the contractility and rhythmicity. The depressant effects of Hycanthone in concentration of 1:1 were compared before and after the topical application of Dyphylline in the above mentioned concentrations. It was found that Dyphylline in concentration of 1.0 mg/1.0 ml could partially antagonize the depressant effect of Hycanthone on the heart rate but not on the force of contraction. Dyphylline in concentration of 10 mg/1.0 ml could partially antagonize the depressant effects of Hycanthone on both of the heart rate and the force of contraction. Dyphylline in concentration of 25 mg/1.0 ml could completely antagonize the depressant effects of hycanthone on both of the heart rate and the force of contraction.

Animals↗

PubMed1987

Probenecid inhibition of the renal excretion of dyphylline in chicken, rat and man.

The effect of probenecid on the renal excretion of dyphylline was studied in chicken, rat and man. Dyphylline was found to be actively excreted when measured by the Sperber preparation in hens, the isolated perfused kidney of the rat and clearance studies in man. In each study probenecid significantly decreased dyphylline excretion demonstrating that dyphylline occupied the renal organic anion transport system. This same drug interaction, at the level of the renal excretory system, in these three species occurred at comparable concentrations of dyphylline and probenecid.

Adult↗

PubMed1983

Dyphylline versus theophylline: a double-blind comparative evaluation.

This study was a randomized double-blind evaluation of three doses of dyphylline, theophylline, and placebo for blocking exercise-induced bronchospasm (EIB). Twenty patients aged 12 to 17 years took one of the following on five separate days prior to an exercise challenge: 10, 15, or 20 mg/kg dyphylline; 6 mg/kg anhydrous theophylline; or placebo. Linear relationships were found between the log of dyphylline doses and per cent changes from baseline for PEFR, FEV1 and FEF25-75%. The 15 and 20 mg/kg doses differed significantly from placebo in preventing declines in PEFR, FEV1, and FEF25-75%. While significant, these changes were one half to one third those found with 6 mg/kg theophylline. Tremor was twice as common with theophylline. While dyphylline has therapeutic effectiveness compared to placebo for blocking EIB, its benefit is small. Further evaluations are needed to elucidate optimal dosaging for maximal effectiveness.

Adolescent↗

PubMed1985

Theophylline and dyphylline pharmacokinetics in the horse.

The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 hours. Clearance was 42.3 to 69.2 ml/hr/kg. The initial distribution phase was rapid (t1/2 approx 3.5 to 4 minutes); a 2nd distribution phase was slower (t1/2 approx 1.5 to 2 hours). Plasma concentrations of theophylline were in the assumed effective range (10 to 20 micrograms/ml) from 15 minutes until 40 minutes after time zero. The mean apparent volume of distribution was 1.02 L/kg. After bolus IV injection of dyphylline (20 mg/kg), pharmacokinetics were best described by a 2-compartment open model in 2 horses and by a 3-compartment open model in 4 horses. In the 6 horses, elimination half-life of dyphylline was 1.9 to 2.9 hours, and clearance was 200 to 320 ml/hr/kg. Plasma concentrations (approx 50 micrograms/ml) were observed at 10 minutes after injection without adverse effects. Concentrations greater than 10 micrograms/ml were observed from time zero to about 1.5 hours after injection. Theophylline induced significant increases in heart rate, but dyphylline did not affect heart rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗

PubMed1977

Bioavailability of a sustained-release dyphylline formulation.

The bioavailability of dyphylline from sustained-release tablets, studied in seven normal subjects given a single dose of the drug, was 67.8 per cent of that from conventional tablets. In three subjects given 40 mg/kg dyphylline as sustained-release tablets every 8 hours for four days, serum dyphylline concentrations were maintained above 7.88 microng/ml once steady state was achieved. No adverse effects were noted, though in one subject peak serum dyphylline concentrations reached 30 microng/ml after multiple doses.

Adult↗

PubMed1981

Dyphylline elimination kinetics in lactating women: blood to milk transfer.

A population of 20 normal lactating females between the ages of 20 and 35 years was treated with a single 5 mg/kg intragluteal dose of dyphylline, 7-(2,3-dihydroxypropyl)theophylline. The distribution of the drug between blood and milk and its pharmacokinetics of elimination were determined. The apparent volume of distribution (Vd) of dyphylline was found to be 0.505 +/- 0.162 l./kg, the elimination rate constant (Kel) was 0.228 +/- 0.055 hr-1, the biological half-life (t1/2) was 3.21 +/- 0.76 hr, and the total body clearance (CI) was 0.109 +/- 0.036 l./kg/hr. The ratio described by dyphylline distribution between milk and serum (M/S) was 2.08 +/- 0.52. The elimination rate from milk was equivalent to that from blood.

Adult↗

PubMed1985

Preparation and characterization of potential prodrugs of dyphylline.

Four diesters and four monoesters of dyphylline were synthesized as prodrugs proposed to prolong the duration of action of dyphylline. They were characterized by IR, 1H NMR, HPLC, and MS. Appropriate solvent-programming conditions for the HPLC separation of dyphylline and the newly synthesized mono- and diesters were developed. It was confirmed by low-temperature 1H NMR at approximately -40 degrees C that all four monoesters were located on the primary hydroxy position. Attempts to produce the secondary monoesters yielded the primary monoesters during purification. Monoesters were shown by HPLC and MS to migrate between the primary and secondary hydroxy groups in aqueous solution.

Chemistry, Pharmaceutical↗

PubMed1983

Pharmacokinetics and bioavailability of three dyphylline preparations.

The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg X kg-1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16 +/- 0.18 h and for the tablet 2.59 +/- 0.56 h. The mean clearance rate for S was 13.6 +/- 1.7 h-1 and volume of distribution 43.0 +/- 3.91. Peak concentration (Cmax, micrograms X ml-1), time of peak (Tmax, h), area under the curve (AUC, micrograms X ml-1 X h) and relative bioavailability (RB, %), were determined for three preparations: Cmax S, 33.7 +/- 3.7; R, 27.7 +/- 4.2; SR, 10.4 +/- 1.5 Tmax: S, 0.33 +/- 0.0; R, 0.66 +/- 0.0; SR, 2.13 +/- 1.1 AUC: S, 108.4 +/- 12.1; R, 113.9 +/- 25.2; SR, 104.0 +/- 30.8 RB: Reference Product R, 105.00 +/- 16.00; SR, 100.00 +/- 25.00 The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg X kg-1 dose and establish bioequivalence for the products studied.

Adult↗

PubMed2002

Kinetic-spectrophotometric determination of theophylline, dyphylline, and proxyphylline by use of partial least-squares regression.

A kinetic-spectrophotometric method for the determination of theophylline, dyphylline and proxyphylline, based on their azo coupling reaction with the diazonium ion of sulfanilic acid after a treatment with alkali, is proposed. The absorbance is recorded from 340 to 600 nm every second during reaction for 90 s, and calibration is performed by partial least-squares regression, using first derivative spectra values. Mixtures containing 2.5-13 micro g mL(-1) dyphylline and proxyphylline, and 2-9 micro g mL(-1) theophylline were successfully resolved with root mean squared errors of prediction (RMSEP) of 0.4, 0.3, and 0.2 for dyphylline, proxyphylline, and theophylline, respectively. The proposed method was satisfactorily applied to the determination of the three compounds in a commercially available pharmaceutical preparation and provided results similar to those obtained by HPLC.

Aminophylline↗

PubMed1980

Utilization of intravenous dihydroxypropyl theophylline (dyphylline) in an aminophylline-sensitive patient, and its pharmacokinetic comparison with theophylline.

The pharmacokinetics and urinary excretion of intravenously administered 7-(2,3-dihydroxypropyl) theophylline (dyphylline), were studied in a 37-yr-old asthmatic woman with ethylene diamine sensitivity who manifested intolerance to intravenous aminophylline on three separate occasions. In this subject, intravenously administered dyphylline was tolerated very well and was effective in the subsequent management of acute bronchospastic episodes. Dyphylline was significantly concentrated in the urine. This, coupled with its rapid clearance, suggests potential clinical application in patients with hepatic dysfunction. Though aminophylline sensitivity is rare, ethylene diamine sensitivity should be considered in untoward reactions to this drug.

Adult↗