Tramadol and o-desmethyl tramadol clearance maturation and disposition in humans: a pooled pharmacokinetic study.

Background And Objectives: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition.

Methods: Tramadol and O-desmethyl tramadol (M1) observations in 295 human subjects (postmenstrual age 25 weeks to 84.8 years, weight 0.

Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist.

Cebranopadol (trans-6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1'(3'H)-pyrano[3,4-b]indol]-4-amine) is a novel analgesic nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonist [Ki (nM)/EC50 (nM)/relative efficacy (%): human NOP receptor 0.9/13.0/89; human mu-opioid peptide (MOP) receptor 0.

Investigations into the drug-drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes.

The new analgesic tapentadol was evaluated for induction and inhibition of several cytochrome P450 enzymes in vitro, and protein binding was assessed. It was concluded that no clinically relevant drug-drug interactions are likely to occur through either mechanism.

Semi-mechanistic pharmacokinetic/pharmacodynamic modelling of the antinociceptive response in the presence of competitive antagonism: the interaction between tramadol and its active metabolite on micro-opioid agonism and monoamine reuptake inhibition, in the rat.

Purpose: To establish a semi-mechanistic pharmacokinetic/pharmacodynamic (pk/pd) model for racemic tramadol (T) integrating all the components with a significant contribution to T effects in rats, using cold allodynia in the Bennett model of neuropathic pain.

Methods: Male Sprague-Dawley rats (n=53) were randomly allocated in six groups receiving saline, racemic T (5 mg/kg), RR-T (5 mg/kg), SS-T (5 mg/kg), RR-O-demethyltramadol [RR-M1 (1 mg/kg)] or SS-M1 (30 mg/kg) in two h intravenous infusion.

Results: The mu-opioid effects of RR-M1 (E(RR-M1)) were described with an effect compartment model.

Peritoneal microdialysis in freely moving rodents: an alternative to blood sampling for pharmacokinetic studies in the rat and the mouse.

By performing microdialysis in the peritoneal cavity, we studied the pharmacokinetics of Tramadol in awake, freely moving small laboratory animals. The systemic exposure to Tramadol was determined using both microdialysis sampling and collection of whole blood following a single intravenous injection (10 mg/kg) or a single oral dose (100 mg/kg) of Tramadol HCl. The sampling frequency of the dialysate was 10 min (mouse study) or 20 min (rat study).