Midazolam drug administration route

Drug administration route Intranasal midazolam is used widely and successfully as pre-medication, particularly in children, avoiding first-pass metabolism and increasing systemic availability [29" ]. 

Most BZs are completely absorbed from the gastrointestinal (GI) tract. The one exception is clorazepate, a pro-drug that undergoes acid hydrolysis in the stomach and is decarboxylated to form N-desmethyl-diazepam, which is then completely absorbed into the bloodstream (Bellantuono et ak, 1980 Hobbs et ak, 1996 Chouinard et ak, 1999). In contrast, most BZs, with the exception of lorazepam and midazolam, are not consistently absorbed from intramuscular injection (Chouinard et ak, 1999). Lorazepam is available as a sublingual form that reaches clinical effect at the same rate as an oral dose. In general, intravenous administration is used only for anesthesia or for the acute management of seizures. When BZs are given via this route, the onset of action is almost immediate (Chouinard et ak, 1999). 

Midazolam, Triazolam, and Flurazepam The feasibility of intranasal administration of midazolam, flurazepam, and triazolam has been studied and compared with oral absorption in dogs. There was a 3.4-fold increase in the Cmax after nasal administration, from 5.5-8.7ng/mL to 17.4-30.0 ng/mL. The mean tm showed comparable values for both routes. The Tnmx obtained after nasal administration of midazolam was found to be 15 min, as compared with the 15-45 min observed for oral dosing, while the Cmax after nasal administration was 6.5-20.3 ng/mL, as compared with 3.0-8.6ng/mL observed for the oral route. Like midazolam and triazolam, flurazepam also showed a shorter half-life, 15 min, as compared with 15 15 min with oral administration. The Cmax for oral administration was 0.14-0.59 ng/mL after nasal administration it was in the range of 2.6-11.1 ng/mL, a 16.4-fold increase. Since the gastrointestinal tract at bedtime is likely to be in the fed state, causing a twofold decrease in the absorption of midazolam and triazolam, the nasal route may be a better option for the treatment of amnesia, since these drugs cross the nasal mucosa effectively without the use of an absorption enhancer, as shown in these studies [108],... 

Research is needed to improve the delivery of drugs in children, either to enhance compliance via the route of choice or to identify alternative routes where the normal route of administration is unavailable or associated with severe side effects. The efficacy of administering ketamine and midazolam orally, rectally and intravenously to children receiving invasive procedures has been compared (Ozdemir et al., 2004). It was found that the alternatives routes were equally effective. The use of other routes may mitigate the usual prolonged sedation and psychedelic effects of intravenous administration of ketamine/midazolam in children. 

---