PMID- 17614227
OWN - NLM
STAT- MEDLINE
DCOM- 20071018
LR  - 20181201
IS  - 1872-6283 (Electronic)
IS  - 0379-0738 (Linking)
VI  - 170
IP  - 2-3
DP  - 2007 Aug 6
TI  - Interactions between 3,4-methylenedioxymethamphetamine, methamphetamine, 
      ketamine, and caffeine in human intestinal Caco-2 cells and in oral 
      administration to rats.
PG  - 183-8
AB  - Amphetamine-type stimulants (ATSs) are often abused orally in the form of tablets 
      for recreational purposes. The ATS tablets contain one or more active ingredients 
      such as 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (MA), ketamine 
      (KA), and caffeine (CF). The aim of this work is to determine whether such 
      components in tablets interact with each other in intestinal absorption. The 
      interactions between MDMA, MA, KA, and CF in the uptake and permeation by human 
      intestinal epithelial Caco-2 cell line were investigated in monolayer cultures. 
      MDMA, MA, and KA mutually inhibited the uptakes by Caco-2 cells. The inhibition 
      of MA uptake by KA was the greatest of all combinations (72.6% inhibition). 
      Similarly, MDMA, MA, and KA mutually inhibited the permeation from the apical to 
      the basolateral side through Caco-2 cells. Although CF did not affect the uptakes 
      of MDMA, MA, and KA, CF enhanced the permeation of MDMA in comparison to MDMA 
      alone. In addition, the interaction of MA with KA and that of MDMA with CF in 
      intestinal absorption were investigated by oral administration to rats. The area 
      under the plasma concentration-time curve of MA significantly decreased by 
      co-administration with KA in comparison to MA alone, while that of MDMA 
      significantly increased by co-administration with CF in comparison to MDMA alone. 
      The results in rats were similar to those in Caco-2 cells. These findings suggest 
      that the intestinal absorption of similar compounds with amine moieties such as 
      MDMA, MA, and KA are mediated by a common transport system, and that CF affects 
      the absorption of MDMA in a different way from the transport system. In human, 
      intakes of ATS tablets mixed with such components might result in similar 
      interactions in intestinal absorption to those in Caco-2 cells and rats.
FAU - Kuwayama, Kenji
AU  - Kuwayama K
AD  - National Research Institute of Police Science, Kashiwanoha, Kashiwa, Chiba, 
      Japan. kuwayama@nrips.go.jp <kuwayama@nrips.go.jp>
FAU - Inoue, Hiroyuki
AU  - Inoue H
FAU - Kanamori, Tatsuyuki
AU  - Kanamori T
FAU - Tsujikawa, Kenji
AU  - Tsujikawa K
FAU - Miyaguchi, Hajime
AU  - Miyaguchi H
FAU - Iwata, Yuko
AU  - Iwata Y
FAU - Miyauchi, Seiji
AU  - Miyauchi S
FAU - Kamo, Naoki
AU  - Kamo N
FAU - Kishi, Tohru
AU  - Kishi T
LA  - eng
PT  - Journal Article
DEP - 20070705
PL  - Ireland
TA  - Forensic Sci Int
JT  - Forensic science international
JID - 7902034
RN  - 0 (Anesthetics, Dissociative)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Hallucinogens)
RN  - 3G6A5W338E (Caffeine)
RN  - 44RAL3456C (Methamphetamine)
RN  - 690G0D6V8H (Ketamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Administration, Oral
MH  - Anesthetics, Dissociative/administration & dosage/blood/pharmacokinetics
MH  - Animals
MH  - Area Under Curve
MH  - Caco-2 Cells/*metabolism
MH  - Caffeine/administration & dosage/blood/*pharmacokinetics
MH  - Cells, Cultured
MH  - Central Nervous System Stimulants/administration & dosage/blood/pharmacokinetics
MH  - Drug Interactions
MH  - Forensic Toxicology
MH  - Hallucinogens/administration & dosage/blood/pharmacokinetics
MH  - Humans
MH  - Intestinal Absorption/drug effects
MH  - Intestinal Mucosa/*metabolism
MH  - Ketamine/administration & dosage/blood/*pharmacokinetics
MH  - Male
MH  - Methamphetamine/administration & dosage/blood/*pharmacokinetics
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & 
      dosage/blood/*pharmacokinetics
MH  - Rats
MH  - Rats, Wistar
EDAT- 2007/07/07 09:00
MHDA- 2007/10/19 09:00
CRDT- 2007/07/07 09:00
PHST- 2006/08/30 00:00 [received]
PHST- 2007/02/14 00:00 [revised]
PHST- 2007/02/15 00:00 [accepted]
PHST- 2007/07/07 09:00 [pubmed]
PHST- 2007/10/19 09:00 [medline]
PHST- 2007/07/07 09:00 [entrez]
AID - S0379-0738(07)00567-1 [pii]
AID - 10.1016/j.forsciint.2007.02.034 [doi]
PST - ppublish
SO  - Forensic Sci Int. 2007 Aug 6;170(2-3):183-8. doi: 
      10.1016/j.forsciint.2007.02.034. Epub 2007 Jul 5.