Evidence map›Paper›PMID 25301936›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2014

Enhanced methamphetamine metabolism in rhesus macaque as compared with human: an analysis using a novel method of liquid chromatography with tandem mass spectrometry, kinetic study, and substrate docking.

Ravinder Earla, Santosh Kumar, Lei Wang, Steven Bosinger, Junhao Li, Ankit Shah, Mohitkumar Gangwani, Anantha Nookala, Xun Liu, Lu Cao and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Ravinder EarlaDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.) earlar@umkc.edu ksantosh@uthsc.edu.
Santosh KumarDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.) earlar@umkc.edu ksantosh@uthsc.edu.
Lei WangDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Steven BosingerDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Junhao LiDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Ankit ShahDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Mohitkumar GangwaniDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Anantha NookalaDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Xun LiuDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Lu CaoDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Austin JacksonDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Peter S SilversteinDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Howard S FoxDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Weihua LiDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
Anil KumarDivision of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri (R.E., A.S., M.K.G., A.N., X.L., L.C., A.J., P.S.S., A.K.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences, Memphis, Tennessee (S.K.); Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China (L.W., J.L., W.L.); Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (S.B.); University of Nebraska Medical Center, Omaha, Nebraska (H.S.F.).
University of Missouri–Kansas City · USUniversity of Nebraska Medical Center · USEast China University of Science and Technology · CNEmory University · USUniversity of Tennessee Health Science Center · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
Methamphetamine and AIDS in a Non-Human Primate ModelR01DA025011 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, ANIL · 2008 to 2014
$1.8M
HIV, Drug Abuse and NeurotoxicityR01DA025528 · NIDA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KUMAR, ANIL · 2009 to 2013
$1.4M
NIDA NIH HHS DA025011NIDA NIH HHS DA025528NIDA NIH HHS R01 DA025011NIDA NIH HHS R01 DA025528NIH HHS P51 OD011132
6 · The paper itself

Abstract

Methamphetamine (MA), which remains one of the widely used drugs of abuse, is metabolized by the cytochrome P450 (P450) family of enzymes in humans. However, metabolism of methamphetamine in macaques is poorly understood. Therefore, we first developed and validated a very sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method using solid phase extraction of rhesus plasma with a lower limit of quantitation at 1.09 ng/ml for MA and its metabolites, 4-hydroxy methamphetamine (4-OH MA), amphetamine (AM), 4-OH amphetamine (4-OH AM), and norephedrine. We then analyzed plasma samples of MA-treated rhesus, which showed >10-fold higher concentrations of AM (∼29 ng/ml) and 4-OH AM (∼28 ng/ml) than MA (∼2 ng/ml). Because the plasma levels of MA metabolites in rhesus were much higher than in human samples, we examined MA metabolism in human and rhesus microsomes. Interestingly, the results showed that AM and 4-OH AM were formed more rapidly and that the catalytic efficiency (Vmax/Km) for the formation of AM was ∼8-fold higher in rhesus than in human microsomes. We further examined the differences in these kinetic characteristics using three selective inhibitors of each human CYP2D6 and CYP3A4 enzymes. The results showed that each of these inhibitors inhibited both d- and l-MA metabolism by 20%-60% in human microsomes but not in rhesus microsomes. The differences between human and rhesus CYP2D6 and CYP3A4 enzymes were further assessed by docking studies for both d and l-MA. In conclusion, our results demonstrated an enhanced MA metabolism in rhesus compared with humans, which is likely to be caused by differences in MA-metabolizing P450 enzymes between these species.

Indexed as

AmphetamineAnimalsChromatography, LiquidCytochrome P-450 CYP2D6Cytochrome P-450 CYP3AHumansKineticsMacaca mulattaMethamphetamineMicrosomes, LiverPhenylpropanolamineTandem Mass SpectrometryAmphetamineCytochrome P-450 CYP2D6Cytochrome P-450 CYP3AMethamphetaminePhenylpropanolamine

Identifiers

PMID25301936
PMCPMC4244873
OpenAlexW2318145128

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.