Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics.
The kinetics of temazepam, 30 mg, were evaluated in 11 patients with end-stage renal disease. Age ranged from 18 to 65 years. On two occasions separated by 1 week, single oral 30 mg doses of temazepam were given once with water (TM) and once with 3600 mg aluminum hydroxide gel (TM + AHG). There were no significant differences in the maximum plasma concentration, the time to reach maximum concentration, or elimination rates between TM and TM + AHG dosing. In approximately half the subjects there were secondary temazepam peak concentrations. In the remaining subjects, temazepam elimination was biphasic, with the terminal t1/2 ranging from 11 to 77 hours. There was a lag time before absorption in all subjects. The percent free temazepam in plasma from dialysis subjects ranged from 4.4% to 8.8% (mean = 5.9%). Compared with literature reports of subjects with normal renal function, the maximum plasma concentration was lower and the percent free temazepam was higher in dialysis subjects. When sedation score was plotted against plasma temazepam concentration, there was clockwise hysteresis consistent with tolerance or adaptation to effects of the drug. Thus aluminum hydroxide gel does not affect temazepam absorption. The clinical significance of the low plasma concentrations and high free temazepam fraction in dialysis subjects is uncertain.
Kroboth
P D
PD
Smith
R B
RB
Rault
R
R
Silver
M R
MR
Sorkin
M I
MI
Puschett
J B
JB
Juhl
R P
RP
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis; D013693:Temazepam / Q000097:blood / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D000536:Aluminum Hydroxide; D013693:Temazepam