A Single‐Blind, Crossover Comparison of the Pharmacokinetics and Cognitive Effects of a New Diazepam Rectal Gel with Intravenous Diazepam

• Published in: Epilepsia (Copenhagen) Vol. 39; no. 5; pp. 520 - 526
• Main Authors: Cloyd, James C., Lalonde, Richard L., Beniak, Thomas E., Novack, Gary D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-05-1998; Blackwell
• Subjects: Administration, Rectal; Anticonvulsants. Antiepileptics. Antiparkinson agents; Area Under Curve; Biological and medical sciences; Cognition - drug effects; Cognitive effects; Cross-Over Studies; Diastat; Diazepam; Diazepam - administration & dosage; Diazepam - pharmacokinetics; Diazepam - pharmacology; Diazepam rectal gel; Drugs, Generic; Gels; Humans; Male; Medical sciences; Neuropharmacology; Neuropsychological Tests; Pharmacokinetics; Pharmacology. Drug treatments; Single-Blind Method; Human; Intravenous administration; Psychotropic; Male; Psychometrics; Anticonvulsant; Cognition; Route of administration; Crossover study; Rectal administration; Chemotherapy; Absorption; Dosage form; Adult; Benzodiazepine derivatives; Biological effect; Pharmacokinetics; Diazepam; Comparative study; Freeze
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1157.1998.tb01415.x

Purpose: The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat®) with intravenously administered DZP.
Methods: Twenty healthy volunteers were enrolled in a single‐blind, randomized, double‐dummy, two‐period, crossover study. Subjects received either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood samples for DZP and desmethyldiazepam analysis were obtained before the dose and from 3 min to 240 h after the dose. Heart rate and blood pressure were measured over the first 24‐h period. Subjects also completed five repetitions of a neuropsychological test battery over the first 8‐h period.
Results: Diazepam rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second maximum of 447 ± 91.1 ng/ml at ∼70 min. The absolute bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP were less alert and performed less efficiently on the WAIS Digit Symbol test 6 min after the dose. Subjects receiving DZP rectal gel performed less well on the WAIS Digit Span test 1 h after the dose and required more time to complete the Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug administration.
Conclusions: Diastat® displayed rapid, consistent absorption and was well tolerated. Alterations in cognition were mild and dissipated within 4 h of drug administration. This new rectal drug‐delivery system offers an easy, safe, and bioavailable method to administer DZP.