Serum Theophylline Concentrations in very Preterm Neonates Receiving Intravenous Aminophylline for Apnea

Objective: To determine the percentage of neonates who achieved therapeutic theophylline level (TTL) after receiving standard IV loading/maintenance aminophylline doses. To assess factors associated with achieving therapeutic theophylline concentrations and to describe adverse effects of aminophylline.Materials and Methods: This was a pilot, cross-sectional study. Preterm neonates ≤34 weeks’ gestation for which aminophylline was indicated for treatment of apnea were enrolled. Standard IV aminophylline dosage is 8 mg/kg loading dose, followed by 1.5 mg/kg maintenance dose every 8 hours. Serum theophylline concentrations were measured prior to the 8th maintenance dose. Descriptive statistics, univariate and multivariate analyses were performed.Results: Twenty-five neonates (52% female) were enrolled: mean (standard deviation) gestational age and birth weight were 30.4 (2) weeks and 1,277 (415) grams, respectively. Aminophylline was initiated at a median (25%tile, 75%tile) postnatal age of 4 (1, 8) days. Baseline heart rate prior to the loading dose was 153 (13) beats-per-minute. Sixty percent of neonates achieved a therapeutic theophylline level. In the univariate analysis, being male and postnatal age ≤5 days were associated with successfully achieving a TTL. After adjusting for gender, postnatal age ≤5 days was the only factor associated with achieving a TTL (adjusted odds ratio 17.7, 95% confidence interval: 1.9, 164.4). Tachycardia and feeding intolerance were observed in 44% and 24% of neonates, respectively.Conclusion: Current IV aminophylline dosing conditions in Thailand achieved TTL in approximately two-thirds of neonates, suggesting therapeutic drug monitoring is beneficial for guiding dosing. A higher maintenance dose could be considered for neonates older than 5 days.

Serum theophylline after multiple dosing with transdermal gels in cats

Objectives Our objectives were, first, to determine if therapeutic serum theophylline concentrations could be achieved using long-term, once-daily dosing of transdermal theophylline and, secondarily, to evaluate the difference between two transdermal theophylline formulations. Methods Seven healthy cats, 1–10 years of age, were evaluated in a two-way, randomized, double-blinded, crossover study. Participants received transdermal theophylline at 15 mg/kg for 21 days in either pluronic lecithin organogel (PLO) or Lipoderm formulation. On day 22, blood was collected 2, 6, 14 and 24 h after dosing. After a 14 day washout period, blood was collected to verify non-detectible theophylline concentrations. The alternate formulation was administered for 21 days, and sampling was repeated. Serum theophylline concentrations were determined using an automated immunoassay. Serum concentrations were compared between formulations using a two-way random-measures ANOVA and over time within a formulation using a repeated-measures ANOVA. Results Therapeutic serum theophylline concentrations were achieved for 2/7 cats in each group. Of 56 serum theophylline measurements obtained, only seven (13%) were within the therapeutic range. No significant difference was detected in drug concentrations achieved by the transdermal formulations at any time point. In addition, no significant difference in serum theophylline concentrations was noted between time points for PLO ( P = 0.751) or Lipoderm ( P = 0.107). Conclusions and relevance Once-daily transdermal dosing of theophylline does not reliably achieve therapeutic concentrations. Individual cats may achieve therapeutic concentrations. No significant difference was noted between PLO and Lipoderm formulations. Therefore, transdermal theophylline formulations should not be considered as a first-line therapy in feline asthma patients.

The new trends in theophylline therapy

Sustained-release theophylline pellets formulation for once-daily evening administration significantly improved patients compliance and adjusted serum levels profile of the drug. The patients conversion from i.v. to p.o. therapy is one of the most critical steps in the treatment of asthma according to its chronopathophysiological character. In our study we have examined safety and efficiency of this conversion in twelve hospitalised asthmatic patients who were given the new sustained-release theophylline pellets formulation for once-daily evening administration. The lung function parameters (FEV1, VC, RV, and Rt) and serum theophylline concentrations were monitored. So, the values obtained for the last day of i.v. therapy and the fifth day of p.o. therapy were compared. We found that 75% of the patients had no change or improved lung function on the conversion. Our results indicate that this conversion from i.v. to p.o. theophylline therapy is safe and could be efficacious. Also, the maximum theophylline serum levels could safely be predicted by measuring only one serum concentration in p.o. therapy with sustained-release theophylline pellets formulation for once-daily evening administration.

Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination

A glass microchip is described in which reagents and serum samples for competitive immunoassay of serum theophylline can be mixed, reacted, separated, and analyzed. The device functions as an automated microfluidic immunoassay system, creating a lab-on-a-chip. Electroosmotic pumping was used to control first the mixing of 50-fold-diluted serum sample with labeled theophylline tracer in a 1:1 ratio, followed by 1:1 mixing and reaction with anti-theophylline antibody. The 51-nL on-chip mixer gave the same concentration as dilution performed off-chip, within 3%. A 100-pL plug of the reacted solution was then injected into an electrophoresis separation channel integrated within the same chip. Measurements of free and bound tracer by fluorescence detection gave linear calibration curves of signal vs log[theophylline] between 0 and 40 mg/L, with a slope of 0.52 ± 0.03 and an intercept of −0.04 ± 0.04 after a 90-s reaction time. A detection limit of 0.26 mg/L in serum (expressed before the dilution step, actual concentration of 1.3 μg/L at the detector) was obtained. Recovery values were 107% ± 8% for 15 mg/L serum samples.