The influence of particle size on the bioavailability of inhaled temazepam.
1. Temazepam was administered by aerosol using a standard protocol to healthy volunteers. Two studies are reported in which different dosage formulations were used: a) 30 mg of the 5 mu diameter particle (n = 6); b) 10 mg of the 2 mu diameter particle (n = 6). 2. An open crossover design was followed in each study. On one occasion in both studies subjects used a gargling procedure to remove drug which had been deposited in the mouth and oropharynx. 3. Serial venous blood samples were drawn for a period of 24 h. The mean total AUC of the 5 mu preparation was significantly reduced by gargling (3153 ng ml-1 h to 1066 ng ml-1 h) (F = 0.32). Gargling also had a significant effect on the mean AUC(0-1 h). 4. In contrast gargling had no significant effect on the mean AUC associated with the smaller diameter particle preparation (630 ng ml-1 h) vs 397 ng ml-1 h (F = 0.74). 5. These findings also indicate that temazepam deposition in the pulmonary tree is enhanced by the use of a 2 mu rather than a 5 mu diameter particle. However, the plasma drug concentrations achieved are unlikely to produce a sufficiently marked sedative effect for endoscopic investigations such as gastroscopy.
Fee
J P
JP
Department of Anaesthetics, Queen's University of Belfast, Northern Ireland.
Collier
P S
PS
Launchbury
A P
AP
Clarke
R S
RS
D000280:Administration, Inhalation; D000328:Adult; D001682:Biological Availability; D006801:Humans; D008297:Male; D010316:Particle Size; D012016:Reference Values; D013693:Temazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D013693:Temazepam