Pyridoxine as therapy in theophylline-induced seizures.
Theophylline-induced seizures have significant morbidity and mortality and are difficult to treat. Theophylline therapy for asthma has been observed to depress plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric acid (GABA) synthesis and thereby contribute to seizures. We hypothesized that treatment with pyridoxine might prove beneficial in theophylline-induced seizures. One hundred thirty-nine mice were injected with 250 mg theophylline/kg ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment. Decreased rates of seizure (42 vs 70%, p < 0.002) and death (29 vs 56%, p < 0.002) were observed. Six New Zealand White rabbits were given 115 mg theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min. Serum theophylline levels and plasma PLP levels showed significant negative correlation prior to pyridoxine infusion with a mean peak theophylline level of 182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG) tracings were obtained before infusions, during theophylline infusion and during pyridoxine infusion. All 6 rabbits developed abnormal EEGs during theophylline infusion and all 6 rabbit EEG patterns returned to baseline during treatment with pyridoxine. These findings suggest that pyridoxine may partially reverse theophylline-induced central nervous system toxicity.
Walter Reed Army Institute of Research, Washington, DC, USA.
G M
GM
Glenn
M S
MS
Krober
P
P
Kelly
J
J
McCarty
M
M
Weir
D000628:Aminophylline / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D011732:Pyridoxal Phosphate / Q000097:blood; D011736:Pyridoxine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D013045:Species Specificity; D013806:Theophylline / Q000097:blood
D001993:Bronchodilator Agents; D000628:Aminophylline; D011732:Pyridoxal Phosphate; D013806:Theophylline; D011736:Pyridoxine