The relationship of cerebrospinal fluid and plasma theophylline concentrations in children and adolescents taking theophylline

Auritt, William A.; McGeady, Stephen J.; Mansmann, Herbert C.

doi:10.1016/0091-6749(85)90102-2

Cited by 14 publications

(6 citation statements)

References 7 publications

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“…Theophylline readily crosses the bloodbrain barrier. One study found a linear relationship between serum and CSF theophylline concentrations in children (Auritt et al 1985).…”

Section: Neurological Effectsmentioning

confidence: 98%

Adverse Reactions and Interactions with Theophylline

Skinner

1990

Drug Safety

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Despite the trend towards newer therapeutic agents, theophylline continues to play a major role in the treatment of reversible airway obstruction. Clinical use of the drug is complicated by a relatively narrow therapeutic range and a large pharmacokinetic variability between patients. Generally, however, theophylline toxicity is foreseeable and preventable. Most cases can be attributed to either inadvertent or intentional overdosing of the drug. Age, disease state and drug interactions are other factors which may contribute to its toxicity. Nausea, vomiting and tachycardia are common signs of mild theophylline toxicity; seizures, ventricular arrhythmias and hypotension are life-threatening manifestations of severe toxicity which may respond poorly to standard therapy. Although serum theophylline concentration correlates with toxicity in a general fashion, life-threatening adverse reactions are not readily predictable from the drug concentration alone. Treatment of theophylline toxicity primarily involves supportive care along with gastric lavage and administration of activated charcoal to facilitate drug removal. The early use of haemoperfusion may be life-saving in cases of severe toxicity.

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“…Theophylline readily crosses the bloodbrain barrier. One study found a linear relationship between serum and CSF theophylline concentrations in children (Auritt et al 1985).…”

Section: Neurological Effectsmentioning

confidence: 98%

Adverse Reactions and Interactions with Theophylline

Skinner

1990

Drug Safety

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“…TP also exerts excitatory influences on the skeletal muscle, gastric secretion, kidneys and fatty acid metabolism in addition to inhibitory effects on smooth muscle. It is well known that excessive administration of TP occasionally produces serious toxicity, including vomiting, tachycardia, and central nervous system excitation including seizures [6,7]. TB almost has the same importance as of TP [8].…”

Section: Introductionmentioning

confidence: 99%

Binding of caffeine, theophylline, and theobromine with human serum albumin: A spectroscopic study

Zhang

Chen

Zhou

et al. 2009

Journal of Molecular Structure

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“…For theophylline, however, there is a blood-brain barrier and the reported brain:blood concentration ratio for theophylline in the adult rat is 0.41 (Arnaud et al, 1982). Auritt et al (1985) reported CSF:plasma ratio of 0.41 for theophylline in adolescents. Steady state brain:plasma ratios, CSF:plasma ratios for theophylline in neonatal rats are significantly higher than the ratios in adult rats.…”

Section: Discussionmentioning

confidence: 96%

“…The reported brain:blood ratios in neonatal rats are between 0.76 and 0.87 (Habgood et al, 1998). Based on data from Auritt et al (1985) (considering CSF:plasma ratio of 0.41) and Shannon (1999) (serum theophylline concentrations, 167-1360 M), the estimated theophylline concentrations in the CSF during toxicity may reach up to 557 M. Since there is greater penetration of theophylline from blood into brain and CSF in the neonatal rats (Habgood et al, 1998), the concentrations that reach in the CSF during toxicity might be greater in the case of neonates. Using an animal model of theophylline-induced seizures, Ramzan and Levy (1986) reported theophylline concentrations of ∼ 1190 to 1380 M in the cerebrospinal fluid of adult rat.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of human TREK-1 channels by caffeine and theophylline

Harinath

Sikdar

2005

Epilepsy Research

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Caffeine (1,3,7-trimethylxanthine) and theophylline (1,3-dimethylxanthine) are used for therapeutic purposes and can cause life-threatening convulsive seizures due to systemic toxicity. The mechanisms for the epileptogenicity of caffeine and theophylline are not clear. TWIK-related K + channels (TREK-1) are highly expressed in the human central nervous system and have a major role in the control of neuronal excitability by regulating the resting membrane potential. In view of their physiological significance, inhibition of TREK-1 channels may be implicated in caffeine-and theophylline-induced seizures. We thus investigated, using whole-cell patch-clamp technique, modulation of hTREK-1 channels expressed in Chinese hamster ovary (CHO) cells by caffeine and theophylline. Caffeine and theophylline produced reversible inhibition of TREK-1 channels in a concentration-dependent manner. The half-maximal inhibitory concentrations (IC 50 ) for caffeine and theophylline were 377 ± 54 M and 486 ± 76 M, respectively. Caffeine and theophylline depolarized the membrane potential of CHO TREK-1 cells in a reversible and concentrationdependent manner. Inhibition by caffeine (5 mM) and theophylline (2 mM) was attenuated in TREK-1 channels with mutation of the PKA consensus sequence at serine 348, suggesting the involvement of cAMP/PKA pathway in the inhibitory process. Inhibition of TREK-1 channels and consequent membrane depolarization may contribute to the convulsive seizures induced by toxic levels of caffeine and theophylline.

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The relationship of cerebrospinal fluid and plasma theophylline concentrations in children and adolescents taking theophylline

Cited by 14 publications

References 7 publications

Adverse Reactions and Interactions with Theophylline

Adverse Reactions and Interactions with Theophylline

Binding of caffeine, theophylline, and theobromine with human serum albumin: A spectroscopic study

Inhibition of human TREK-1 channels by caffeine and theophylline

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