PMID- 37080736
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20240109
IS  - 2769-6677 (Electronic)
IS  - 1559-6109 (Print)
IS  - 1559-6109 (Linking)
VI  - 62
IP  - 3
DP  - 2023 May 1
TI  - The Pharmacokinetics of Subcutaneous Methylnaltrexone Bromide in Rhesus Macaques 
      (Macaca mulatta).
PG  - 260-266
LID - 10.30802/AALAS-JAALAS-22-000111 [doi]
AB  - Opioids are an integral component of pain management for nonhuman primates. These 
      potent analgesics also adverse gastrointestinal (GI) effects that include 
      constipation, bloating, and delayed gastric emptying. Methylnaltrexone bromide 
      (MNTX) is a selective, peripherally acting mu- and kappa-opioid receptor antagonist 
      that can be used to mitigate the GI effects associated with opioid 
      administration. Unlike naltrexone, a similar drug in this class, MNTX possesses 
      an N-methyl-quaternary amine group that prevents it from crossing the blood brain 
      barrier. This blockage allows inhibition of peripheral GI opioid receptors 
      without affecting opioid-mediated analgesia in the central nervous system. We 
      conducted a pharmacokinetic analysis of MNTX in serum and CSF of 6 healthy 
      juvenile male rhesus macaques after subcutaneous administration of a 0.15-mg/kg 
      dose. We hypothesized that the macaques would demonstrate a T(max) of 0.5 h, 
      similar to that of humans, and that no MNTX would be detected in the CSF. This 
      treatment resulted in a peak serum concentration of 114 +/- 44 ng/mL at 0.25 +/- 0.00 
      h; peak CSF at concentrations were 0.34 +/- 0.07 ng/mL at the T(max). These data 
      show that subcutaneous administration of MNTX to rhesus macaques may block 
      peripheral adverse effects of opioids without interfering with their central 
      analgesic effects.
FAU - Jepkes, Sarah
AU  - Jepkes S
AD  - Primate Medicine Services, California National Primate Research Center, 
      University of California, Davis, California.
FAU - Josee-Lemoy, Marie
AU  - Josee-Lemoy M
AD  - Primate Medicine Services, California National Primate Research Center, 
      University of California, Davis, California.
FAU - Knych, Heather
AU  - Knych H
AD  - California Animal Health and Food Safety Lab Molecular Biosciences, University of 
      California, Davis, California.
FAU - de Lucena, Thiago
AU  - de Lucena T
AD  - Division of Economics, San Diego State University, San Diego, California.
FAU - Ardeshir, Amir
AU  - Ardeshir A
AD  - Infectious Disease Unit, California National Primate Research Center, University 
      of California, Davis, California.
FAU - Stockinger, Diane E
AU  - Stockinger DE
AD  - Primate Medicine Services, California National Primate Research Center, 
      University of California, Davis, California.
LA  - eng
GR  - P51 OD011104/OD/NIH HHS/United States
GR  - P51 OD011107/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230420
PL  - United States
TA  - J Am Assoc Lab Anim Sci
JT  - Journal of the American Association for Laboratory Animal Science : JAALAS
JID - 101269489
RN  - 0RK7M7IABE (methylnaltrexone)
RN  - 5S6W795CQM (Naltrexone)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Quaternary Ammonium Compounds)
SB  - IM
MH  - Humans
MH  - Male
MH  - Animals
MH  - *Naltrexone/pharmacology/therapeutic use
MH  - Macaca mulatta
MH  - *Narcotic Antagonists/pharmacology/therapeutic use
MH  - Analgesics, Opioid/pharmacology
MH  - Quaternary Ammonium Compounds/pharmacology/therapeutic use
PMC - PMC10230534
EDAT- 2023/04/21 00:41
MHDA- 2023/05/22 06:42
PMCR- 2023/11/01
CRDT- 2023/04/20 21:12
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/04/21 00:41 [pubmed]
PHST- 2023/04/20 21:12 [entrez]
PHST- 2023/11/01 00:00 [pmc-release]
AID - 2023000260 [pii]
AID - 10.30802/AALAS-JAALAS-22-000111 [doi]
PST - ppublish
SO  - J Am Assoc Lab Anim Sci. 2023 May 1;62(3):260-266. doi: 
      10.30802/AALAS-JAALAS-22-000111. Epub 2023 Apr 20.