Relative Bioavailability of Rectally Administered Phenobarbital Sodium Parenteral Solution

Abstract

Rectal administration of antiepileptic drugs may be a useful alternative route when oral administration is not possible due to illness, surgery, or status epilepticus. Although parenteral administration often replaces oral administration in these circumstances, there is not always a desirable intravenous line available or repeated intramuscular injections may not be practical. The purpose of this study was to determine the relative bioavailability and time course of absorption of the commercially available parenteral phenobarbital sodium solution administered rectally in comparison with the same preparation given intramuscularly. Seven healthy adult volunteers were given phenobarbital 5 mg/kg intramuscularly and rectally five weeks apart. Eighteen blood samples were drawn over 288 hours. Pharmacokinetic parameters following intramuscular versus rectal administration were the following: area under the curve 5916 vs. 5253 μmol⋅h/L; half-life 112 vs. 113 h; time to maximum concentration 2.1 vs. 4.4 h; and maximum serum concentration 36.2 vs. 31.4 μmol/L. Mean relative bioavailability for rectal phenobarbital was 90 percent. Therefore, the parenteral phenobarbital sodium solution given rectally is well absorbed and provides a useful alternative route of administration.