Pharmacokinetics of rectal diazepam in the prevention of recurrent febrile convulsions

• Published in: Brain & development (Tokyo. 1979) Vol. 8; no. 1; pp. 53 - 59
• Main Authors: Minagawa, Kimio, Miura, Hisao, Mizuno, Satoshi, Shirai, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1986; Elsevier Science
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Diazepam; Diazepam - administration & dosage; Diazepam - blood; Diazepam - therapeutic use; Dose-Response Relationship, Drug; febrile convulsions; Humans; Infant; Kinetics; Medical sciences; Neuropharmacology; optimum dosage regimen; pharmacokinetics; Pharmacology. Drug treatments; Prognosis; rectal administration; Rectum; Recurrence; Seizures, Febrile - blood; Seizures, Febrile - drug therapy; Suppositories; pharmacokinetics; optimum dosage regimen; Diazepam; rectal administration; febrile convulsions; Human; Chemotherapy; Nervous system diseases; Convulsion; Anticonvulsant; Recurrent; Metabolism; Pharmacokinetics; Rectal administration; Fever
• ISSN: 0387-7604; 1872-7131
• DOI: 10.1016/S0387-7604(86)80120-6

To determine the optimum dosage schedule for intermittent rectal diazepam in suppository form for the prevention of recurrent febrile convulsions, we studied the pharmacokinetics of diazepam administered in repeated rectal doses. The plasma concentration-time data for diazepam on twice repeated rectal dosing with 0.5 mg/kg at 8-hour intervals in six infants showed that therapeutic plasma levels could be attained within 30 minutes and maintained for the first 24 hours. Most of the observed plasma diazepam levels were found to be within ± one standard deviation of the values calculated from the pharmacokinetic parameters in six other infants with single rectal dosing. Computer-simulated plasma level profile suggested that plasma diazepam levels may reach the toxic range after administration of five or more doses. Twice repeated rectal dosing with 0.5 mg/kg of diazepam in suppository form at 8-hour intervals during the febrile period may be a rational approach for the prevention of recurrent febrile convulsions.