Evaluation with Heart Rate Variability for the Treatment Effect of Aminophylline in Patients with Bradycardia after Cervical Spinal Cord Injury: A Preliminary Study

After cervical spinal cord injury (SCI), the autonomic nervous system (ANS) becomes impaired and then, bradycardia can develop. In view of this, we performed to prescribe aminophylline as pharmacotherapy for bradycardia. The study population consisted of 36 patients with cervical SCI. Bradycardia developed in 20 patients (55.6%), of these patients, 8 showed spontaneous recovery. Twelve patients had persistent bradycardia, therefore, aminophylline was administered at 0.5 mg/kg/hr by intravenous infusion. Their average heart rate increased within 24 hours after the start of infusion. In heart rate variability analysis for 7 preliminarily selected patients, the spectral waveforms of “oligowave type” indicating ANS impairment tended to appear in relatively early phase after injury (i.e., 2 days to 2 weeks after injury), whereas “normal type” was observed in the late phase (i.e., at 4 weeks). “Sympathetic block type” was observed throughout the follow-up period (2 days to 4 weeks). “Sympathetic block type” was also observed in a non-bradycardic patient on day 2. These results underscore the importance of treating ANS impairment with aminophylline while keeping in mind that bradycardia can occur even in post-SCI patients without clinical manifestations.

Pharmacokinetics of aminophylline delivered to the small intestine and colon using remote controlled capsules

Background A patented remote controlled capsule （RCC） has recently been developed to provide noninvasive drug delivery to selected sites in the human gut that allows assessment of regional gastrointestinal （GI） drug absorption under a normal physiological environment. The objective of this study was to investigate the rate and extent of aminophylline absorption after site-specific delivery of the drug in the GI tract using RCC and a magnetic marker monitoring （MMM） technique. Methods This study was conducted in twelve healthy male subjects, in a three-treatment, randomized, crossover manner with a 7-day washout. Eligible subjects received a 150 mg aminophylline dose through an oral administration, or via a remote controlled capsule, delivered to the small bowel or ascending colon. MMM was employed to monitor the GI transit of the RCC, and the radio-frequency signal was used to activate capsules at target sites. Blood samples were obtained at regular intervals until 24 hours post dose/activation. Plasma theophylline concentrations were measured by a TDx~ System Analyzer. A comparison of the PK profile with the oral dosing route of aminophylline was performed after delivery to the small bowel and colon. Results The RCC was well tolerated in volunteers. The mean capsule activation time for the small bowel and ascending colon was 2.07 hours and 6.08 hours post dose. Aminophylline had similar absorption profiles from the small bowel compared with the stomach, with an area under the curve （AUCt） ratio of 92% vs. the stomach, but a lower absorption profile from the ascending colon, with an AUCt ratio of 47.2% vs. the stomach. Conclusions The proprietary of the RCC and MMM technique offer the opportunity to obtain data on the intestinal absorption of a drug in humans under noninvasive conditions. Aminophylline is rapidly and efficiently absorbed from the small bowel. While colonic absorption was limited by the poor water condition although effective absorption was observed from the ascending colon. This provides an opportunity for rational development of modified-release formulations as well as alternative dosage forms.

Adjunctive sepsis therapy with aminophylline(STAP):a randomized controlled trial

Background:Sepsis is a serious disease caused by infection.Aminophylline has anti-asthma and anti-inflammatory effects.We aimed to explore the safety and effect of aminophylline in sepsis.Methods:We conducted a clinical randomized controlled trial involving 100 patients diagnosed with sepsis within 48 h after intensive care unit(ICU)admission in two sites.All patients were randomized in a 1:1 ratio to receive standard therapy with or without aminophylline.The primary clinical outcome was all-cause mortality at 28 days.Results:From September 27,2018 to February 12,2020,we screened 277 septic patients and eventually enrolled 100 patients,with 50 assigned to the aminophylline group and 50 to the usual-care group.At 28 days,7 of 50 patients(14.0%)in the aminophylline group had died,compared with 16 of 50(32.0%)in the usual-care group(P=0.032).Cox regression showed that the aminophylline group had a lower hazard of death(hazard ratio=0.312,95%confidence interval:0.129–0.753).Compared with the usual-care group,patients in the aminophylline group had a longer survival time(P=0.039 by the log-rank test).The effects of aminophylline on vasopressor dose,oxygenation index,and sequential organ failure assessment score were timedependent with treatment.There were no significant differences in total hospitalization days,ICU hospitalization days,and rates of serious adverse events(all P>0.05).No adverse events were observed in the trial.Conclusions:Aminophylline as an adjunct therapy could significantly reduce the risk of death and prolong the survival time of patients with sepsis.Trial registration:ChiCTR.org.cn,ChiCTR1800019173.

Fast Determination of Ethylendiamine in Aminophylline Tablets by Small-sized Capillary Electrophoresis with Amperometric Detection

A novel method for fast determination of ethylendiamine （EDA） in Aminophylline Tablets has been developed by small-sized capillary electrophoresis with amperometric detection （small-CE-AD） coupled with field-amplified sample injection （FASI）. Under the optimum conditions, EDA and four aliphatic diamine homologs （1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane and 1,6-diaminohexane） could be well separated within 6 min at a separation voltage of 2.0 kV in an acetate buffer solution of pH 3.8 with low limit of detection （LOD） of 1.3 × 10^-11 g/mL for EDA （S/N=3）. The proposed method has been successfully applied to direct deter- mination of EDA content in different batches of Aminophylline Tablets. The method does not require off-line preconcentration and derivatization steps, which should find wide application fields including pharmaceuticals as an alternative to conventional and microchip CE approaches.