Animal and clinical studies on rectal administration of a mixed solution of ibuprofen and diazepam / 中华儿科杂志

ABSTRACT

<p><b>OBJECTIVE</b>Seizure is a common emergency in children with complicated pathogeny. Seizures are usually caused by complicated etiology and fever and febrile seizure are the commonest causes. Repeated and permanent seizures can damage the brain. So it is important to take active and effective measures to control seizure and high fever. Because most seizures and fever take place at home or out of hospital and it is difficult to administer drugs intravenously, it is important to explore an easy, safe, quick and effective way to control and prevent both seizure and fever. The present study aimed to explore the efficacy and safety of rectal administration of mixed ibuprofen and diazepam (IBU-DZP) solution.</p><p><b>METHODS</b>(1) Animal study on the pharmacokinetics in rabbits and pharmacodynamics in rats after rectal administration with the mixed solution and on the irritability of the mixed solution to rectum. (2) Clinical study Pharmacokinetics of the mixed solution in children after rectal administration were investigated.</p><p><b>RESULTS</b>(1) Animal study IBU and DZP were both rapidly absorbed from rectum with a peak blood level of (11.7 +/- 1.2) min and (9.4 +/- 2.7) min in rabbits, respectively. The mixed solution could effectively prevent the severity of seizures induced by pentetrazole and significantly suppressed fever induced by yeast. There were no remarkable pathological changes in rectal tissues after repeated rectal administration of the mixed solution. (2) Clinical study IBU and DZP rapidly reached their peak blood levels at about 30 min and 15 min respectively after rectal administration to the children. The peak values were (57.8 +/- 7.9) mg/L and (450.1 +/- 158.7) microg/L, respectively. In fact, both of them reached levels that were much higher than their therapeutic levels in serum just at 5 min after administration, their blood levels were (41.4 +/- 5.5) mg/L and (321.8 +/- 53.9) microg/L, respectively.</p><p><b>CONCLUSIONS</b>IBU-DZP mixed solution administered rectally is an easy, safe, quick and effective way to control and prevent both seizure and fever.</p>