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Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers.
- Source :
-
The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2014 Sep; Vol. 66 (9), pp. 1222-30. Date of Electronic Publication: 2014 Apr 10. - Publication Year :
- 2014
-
Abstract
- Objectives: The aim of this study was to evaluate the influence of poorly controlled type 1 (T1DM) and type 2 diabetes mellitus (T2DM) on the pharmacokinetics and metabolism of tramadol enantiomers in patients with neuropathic pain.<br />Methods: Nondiabetic patients (control group, n = 12), patients with T1DM (n = 9) or T2DM (n = 9), all with neuropathic pain and phenotyped as cytochrome P450 2D6 extensive metabolizers, received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected over a 24-h period.<br />Key Findings: Patients with T1DM showed reduced Cmax of both tramadol enantiomers. The plasma concentrations of the active (+)-M1 were significantly reduced in T1DM (area under the curve plasma concentration versus time (AUC∞ ): 313.1 ng·h/ml) when compared with nondiabetic patients (AUC∞ : 1246.6 ng·h/ml). The fraction unbound of (+)-M1 was increased in patients with T1DM. Patients with T1DM and T2DM showed reduced AUC and increased fraction unbound of (-)-M1.<br />Conclusions: The reduced total plasma concentrations of the active (+)-M1 in patients with T1DM may not be of clinical relevance because they are counterbalanced by the increased fraction unbound.<br /> (© 2014 Royal Pharmaceutical Society.)
- Subjects :
- Adult
Analgesics, Opioid metabolism
Analgesics, Opioid therapeutic use
Area Under Curve
Blood Glucose metabolism
Diabetes Mellitus, Type 1 blood
Diabetes Mellitus, Type 1 complications
Diabetes Mellitus, Type 2 blood
Diabetes Mellitus, Type 2 complications
Female
Humans
Male
Middle Aged
Phenotype
Stereoisomerism
Tramadol metabolism
Tramadol therapeutic use
Analgesics, Opioid pharmacokinetics
Cytochrome P-450 CYP2D6 metabolism
Diabetes Mellitus, Type 1 metabolism
Diabetes Mellitus, Type 2 metabolism
Diabetic Neuropathies drug therapy
Neuralgia drug therapy
Tramadol pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 2042-7158
- Volume :
- 66
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24717054
- Full Text :
- https://doi.org/10.1111/jphp.12255