Pharmacokinetics and dose proportionality of three Tramadol Contramid OAD tablet strengths.
A three-way crossover study in 27 human volunteers was conducted to characterize the pharmacokinetics and to assess the dose proportionality of 100 mg, 200 mg and 300 mg strengths of a novel once-a-day tramadol controlled-release tablet (Tramadol Contramid OAD) following single-dose administration. Serial blood samples were collected at predefined timepoints over a 48 h period and racemic tramadol and O-desmethyltramadol concentrations in plasma were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using noncompartmental methods. Following dose normalization and logarithmic transformation of concentration-dependent parameters, the results were compared using analysis of variance (ANOVA). The residual variability thereby obtained was used to construct 90% classical confidence intervals. The two one-sided tests procedure was used for all pairwise comparisons. Dose proportionality was concluded since the 90% CI for the ratio of geometric means was included in the acceptance range of 0.80-1.25 for all comparisons.
Karhu
David
D
Labopharm Inc., Laval, QC, Canada.
El-Jammal
Ali
A
Dupain
Thibaut
T
Gaulin
Delphine
D
Bouchard
Sylvie
S
D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D011537:Pruritus / Q000139:chemically induced; D013608:Tablets, Enteric-Coated; D053719:Tandem Mass Spectrometry; D014147:Tramadol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D014839:Vomiting / Q000139:chemically induced
D000701:Analgesics, Opioid; D013608:Tablets, Enteric-Coated; D014147:Tramadol; D001219:Aspartate Aminotransferases