PubMed · 14273319
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H J ROBINSON, J A WAGNER. 1965. D. C. CARDIOVERSION CAUSING VENTRICULAR FIBRILLATION.. https://doi.org/10.1097/00000441-196503000-00008
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OBJECTIVE: The present work aimed to estimate the theophylline pharmacokinetic parameters (TH-PKP) in preterm neonates with apnea during the first month of life in order to optimize its dosage regimen. METHODS: Fifty preterm neonates enrolled in the study with recurrent apnea were admitted during 1998-2000 to the Neonatal Intensive Care Unit of Maternity and Children's Hospital, Al-Mosaida, Jeddah, Kingdom of Saudi Arabia. Criteria for this study were preterm with gestational age (GA) of 26-33 weeks (mean +/- SD 30 +/- 3.9). They received TH of 3-6 mg/kg loading dose (LD) followed by maintenance dose (MD) of 0.5 - 3.0 mg/kg/12 hours. Eight of these patients received phenobarbital and 19 received cimetidine concomitantly for at least 7 days. Blood samples were taken one hour post LD and at steady state (Css). Theophylline levels were determined by fluorescence polarization immunoassay. RESULTS: Phenobarbital significantly enhanced TH clearance (CL) and reduced its half-life (t0.5) but cimetidine had no significant effect. Excluding patients receiving phenobarbital. The mean +/- SD TH-PKP were volume of distribution (Vd) = 0.77 +/- 0.25 L/kg; elimination rate constant (Ke) = 0.027 +/- 0.011 h(-1); CL = 0.019 +/- 0.006 L/h/kg, t0.5 = 30.7 +/- 12.1. There was marked intra patient variability in all TH-PKP. CONCLUSION: In view of the results and practical considerations, initial dosage regimen to attain a TH Css level within the therapeutic range (6-12 ug/ml) was suggested: LD 6-7 mg/kg, MD 1.5 - 2.0 mg/kg/12 hours. To compensate for maturation changes or drug interaction, a method, based on estimation of individual TH CL, was described for adjusting MD.
The effects of toluene on the sensitivity to seizures induced by aminophylline were investigated. Mice were pretreated with an ip injection of corn oil or toluene (100-500 mg/kg) followed by a timed intravenous infusion of aminophylline at various time intervals to assess the seizure thresholds and lethal doses. Toluene increased seizure susceptibility to aminophylline in a dose- and time-dependent manner. Toluene-induced enhancement of seizure susceptibility to aminophylline occurred as early as 30 min and persisted for at least 3 days after a single administration of toluene (500 mg/kg). Treatment of benzaldehyde, one of toluene's metabolites, also showed an increase in the susceptibility to aminophylline. The enhancing effect was also observed in caffeine-induced seizures 1 h, but not 1 day after toluene treatment. These results suggest that individuals with toluene exposure may increase the risk for convulsive and even lethal complications associated with the therapeutic use of aminophylline.