Pharmacokinetic aspects of rectal formulations of temazepam.
An in vitro/in vivo study was carried out with different rectal formulations of temazepam. Pharmacokinetic data were determined in a cross-over study in 10 volunteers after rectal administration of 10 mg temazepam as a polyethylene glycol based suppository (selected from in vitro data), a liquid-filled capsule and a micro-enema respectively, using oral administration of a liquid-filled capsule as a reference. Serum levels of temazepam indicate an instantaneous and complete release from the micro-enema (Frel = 0.94 +/- 0.21, Cmax 205 +/- 36.9 micrograms/l, tmax 0.49 +/- 0.31 hour) and a slower but complete release of temazepam from the suppository (Frel = 1.10 +/- 0.25, Cmax 202 +/- 41.3 micrograms/l, tmax 1.48 +/- 0.41 hour). A high interindividual variation in absorption profiles was observed after rectal administration of the liquid-filled capsule (Frel 0.72 +/- 0.36, Cmax 182 +/- 122 micrograms/l, tmax 4.08 +/- 4.28 hour), which makes it less suitable for rectal use. The micro-enema and suppository appear to be useful as rectal formulations for temazepam.
Hanff
L M
LM
Department of Pharmacy, University Hospital Rotterdam, The Netherlands.
Rutten
W J
WJ
D000285:Administration, Rectal; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D005079:Excipients; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011092:Polyethylene Glycols; D012996:Solutions; D013488:Suppositories; D013693:Temazepam / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D002214:Capsules; D005079:Excipients; D012996:Solutions; D013488:Suppositories; D011092:Polyethylene Glycols; D013693:Temazepam