PMID- 22618801
OWN - NLM
STAT- MEDLINE
DCOM- 20130102
LR  - 20220317
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Linking)
VI  - 29
IP  - 9
DP  - 2012 Sep
TI  - Pharmacokinetic and pharmacodynamic modeling of opioid-induced gastrointestinal 
      side effects in patients receiving tapentadol IR and oxycodone IR.
PG  - 2555-64
LID - 10.1007/s11095-012-0786-5 [doi]
AB  - PURPOSE: To understand the relationship between the risk of opioid-related 
      gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone 
      as well as its active metabolite, oxymorphone, using 
      pharmacokinetic/pharmacodynamic models. METHODS: The analysis was based on a 
      study in patients with moderate-to-severe pain following bunionectomy. Population 
      PK modeling was conducted to estimate population PK parameters for tapentadol, 
      oxycodone, and oxymorphone. Time to AEs was analyzed using Cox 
      proportional-hazards models. RESULTS: Risk of nausea, vomiting, and constipation 
      significantly increased with exposure to tapentadol or oxycodone/oxymorphone. 
      However, elevated risk per drug exposure of AEs for tapentadol was ~3-4 times 
      lower than that of oxycodone, while elevated AE risk per drug exposure of 
      oxycodone was ~60 times lower than that for oxymorphone, consistent with reported 
      in vitro receptor binding affinities for these compounds. Simulations show that 
      AE incidence following administration of tapentadol IR is lower than that 
      following oxycodone IR intake within the investigated range of analgesic 
      noninferiority dose ratios. CONCLUSIONS: This PK/PD analysis supports the 
      clinical findings of reduced nausea, vomiting and constipation reported by 
      patients treated with tapentadol, compared to patients treated with oxycodone.
FAU - Xu, Xu Steven
AU  - Xu XS
AD  - Clinical Pharmacology, Advanced PK-PD Modeling and Simulation, Janssen Research 
      and Development, Raritan, New Jersey, USA. sxu26@its.jnj.com
FAU - Etropolski, Mila
AU  - Etropolski M
FAU - Upmalis, David
AU  - Upmalis D
FAU - Okamoto, Akiko
AU  - Okamoto A
FAU - Lin, Rachel
AU  - Lin R
FAU - Nandy, Partha
AU  - Nandy P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120523
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Phenols)
RN  - 0 (Receptors, Opioid, mu)
RN  - CD35PMG570 (Oxycodone)
RN  - H8A007M585 (Tapentadol)
SB  - IM
MH  - Female
MH  - Gastrointestinal Tract/*drug effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oxycodone/*administration & dosage/adverse effects/pharmacokinetics/pharmacology
MH  - Phenols/*administration & dosage/adverse effects/pharmacokinetics/pharmacology
MH  - Proportional Hazards Models
MH  - Receptors, Opioid, mu/antagonists & inhibitors
MH  - Tapentadol
EDAT- 2012/05/24 06:00
MHDA- 2013/01/03 06:00
CRDT- 2012/05/24 06:00
PHST- 2012/01/20 00:00 [received]
PHST- 2012/05/14 00:00 [accepted]
PHST- 2012/05/24 06:00 [entrez]
PHST- 2012/05/24 06:00 [pubmed]
PHST- 2013/01/03 06:00 [medline]
AID - 10.1007/s11095-012-0786-5 [doi]
PST - ppublish
SO  - Pharm Res. 2012 Sep;29(9):2555-64. doi: 10.1007/s11095-012-0786-5. Epub 2012 May 
      23.