Determination of the adsorption of tramadol hydrochloride by activated charcoal in vitro and in vivo.
Although tramadol is one of the most widely used centrally acting analgesics worldwide, no literature is available regarding adsorption of tramadol HCl powder or tablets (Ultram; 50 mg tramadol HCl per tablet) by activated charcoal (AC) for use as potential adjunct treatment of overdose. The present study incorporated a novel combination of in vitro and in vivo methods to investigate this question. Based on a binding curve of tramadol UV absorbance (UV(a); 225 nm) plotted against the amount of AC, the ratio of amount of tramadol completely adsorbed by AC was 0.05 mg/mg. Also based on UV(a), no tramadol was detected in filtrate of slurries in which up to 62 tablets of Ultram were mixed with 50 g AC; 4.6% of unbound tramadol was detected when 100 tablets of Ultram were mixed with AC. The ratio of amount of tramadol completely adsorbed by AC in this test was 0.10. In vivo, co-administration of 0.1 g/ml of AC produced a 13- to 14-fold rightward shift in tramadol's antinociceptive dose-response curve and a 1.6-fold rightward shift in tramadol's lethality dose-response curve.
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. rraffa@nimbus.temple.edu
R B
RB
Raffa
C
C
Wu
D J
DJ
Stone
M R
MR
Borenstein
E E
EE
Codd
T P
TP
Coogan
D000327:Adsorption; D000818:Animals; D000931:Antidotes / Q000737:chemistry* / Q000627:therapeutic use; D002138:Calibration; D002606:Charcoal / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009294:Narcotics / Q000737:chemistry* / Q000633:toxicity; D010147:Pain Measurement / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013535:Suspensions; D013607:Tablets; D014147:Tramadol / Q000737:chemistry* / Q000633:toxicity
D000931:Antidotes; D009294:Narcotics; D013535:Suspensions; D013607:Tablets; D002606:Charcoal; D014147:Tramadol