The effect of rectal pH values on the absorption of methohexital

The factors underlying the unpredictability of the pharmacokinetics of rectally administered methohexitone remain unclear. The "pH partition hypothesis" offers an explanation. We investigated six children with rectal pH values ranging from 7.5 to 9.8, who were given 25 mg/kg methohexitone 10% via the rectal route under general anaesthesia. Blood samples were taken at zero, 3, 5, 7, 10, 15, 20, 30, 40, 60, 90 and 120 min; rectal pH was measured at zero and 1 min. The methohexitone plasma levels reached a maximum (Cmax) of 2.63 micrograms/ml (median) after 17.5 min (median). The elimination half-life ranged from 37 to 218 min. No positive correlation between lower pH and better resorption (AUC and Cmax) was found. The resorption kinetics of rectally administered methohexitone cannot be explained by its electrochemical properties alone.