BIOEQUIVALENCE STUDY OF TRAMADOL + PARACETAMOL (37.5 + 325 MG) IN HEALTHY HUMAN VOLUNTEERS IN FASTING CONDITION
Abstract
The bioequivalence between test and reference Tramadol and Paracetamol (37.5 + 325 mg) tablets was determined in 36 healthy subjects after a single dose in a randomized crossover study under fasting condition. Plasma concentrations were monitored over a period of 24 hour after the drug administration by validated LC/MS/MS analytical method. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, AUC0-t / AUC0-∞, Tmax, Kel and t½ were determined from plasma concentration time profile of both formulations and found to be acceptable. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the test and reference products. The analysis of variance did not show any significant difference between the two formulations and 90 % confidence intervals for the ratio of Cmax (92.29 -104.18 %), AUC0-t (99.52 - 104.11 %) and AUC0-∞ (99.05 - 104.22 %) for tramadol and Cmax (93.56 - 110.27 %), AUC0-t (96.37 - 102.70 %) and AUC0-∞ (97.22-103.28 %) for paracetamol test and reference products were within the 80 – 125 % interval, satisfying the bioequivalence criteria the US Food and Drug Administration Guidelines. These results indicate that the test and the reference products of Tramadol and Paracetamol are bioequivalent.
Keywords:
Bio-equivalence, Body Mass Index, Confidence interval, LC/MS/MSDOI
https://doi.org/10.25004/IJPSDR.2013.050409References
2. Yi S, Chung Y, Kim T, Shin H, Yoon SH, Cho J, Jang I, Shin S, Yu K. Pharmacokinetics of Extended-Release Versus Conventional Tramadol/ Acetaminophen Fixed-Dose Combination Tablets: An Open-Label, 2-Treatment, Multiple-Dose, Randomized-Sequence Crossover Study in Healthy Korean Male Volunteers. Clinical Therapeutics. 2011; 33(6):728-737.
3. Silva MF, Schramm SG, Kano EK, Koono EEM, Porta V, Serra CHR. Bioequivalence Evaluation of Single Doses of Two Tramadol Formulations: A Randomized, Open-Label, Two-Period Crossover Study in Healthy Brazilian Volunteers. Clinical Therapeutics. 2010; 32(4):758-765.
4. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs. 1993; 46(2):313-340.
5. Alloui A, Chassaing C, Schmidt J, Ardid D, Dubray C, Cloarec A, Eschalier A. Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an inflammatory pain model in rats. European Journal of Pharmacology. 2002; 443:71-77.
6. Dogrul A, Seyrek M, Akgul EO, Cayci T, Kahraman S, Bolay H. Systemic paracetamol-induced analgesic and antihyperalgesic effects through activation of descending serotonergic pathways involving spinal 5-HT7 receptors. European Journal of Pharmacology. 2012; 677:93-101.
7. Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, Eschalier A. Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain. 2008; 139:190–200.
8. Perrot S, Krause D, Crozes P, Naim C. Efficacy and Tolerability of Paracetamol/Tramadol (325 mg/ 37.5 mg) Combination Treatment Compared with Tramadol (50 mg) Monotherapy in Patients with Subacute Low Back Pain: A Multicenter, Randomized, Double-Blind, Parallel-Group, 10-Day Treatment Study. Clinical Therapeutics. 2006; 28:1592-1606.
9. Filitz J, Ihmsen H, Gunther W, Troster A, Schwilden H, Schuttler J, Koppert W. Supra-additive effects of tramadol and acetaminophen in a human pain model. Pain. 2008; 136:262–270.
10. Pergolizzi Jr JV, Laar M, Langford R, Mellinghoff H, Merchante IM, Nalamachu S, O’Brien J, Perrot S, Raffa RB. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain. Journal of Pain Research. 2012; 5:327–346.
11. Midha KK, McKay G. Bioequivalence; Its History, Practice, and Future. The AAPS Journal. 2009; 11(4):664-670.
12. Haas JS, Phillips KA, Gerstenberger EP, Seger AC. Potential Savings from Substituting Generic Drugs for Brand-Name Drugs: Medical Expenditure Panel Survey, 1997–2000. Ann Intern Med. 2005; 142:891-897.
13. Drugs@FDA Glossary of Terms. Available at: http://www.fda.gov/Drugs/InformationOnDrugs/ucm079436.htm#TE. Accessed April 19, 2013
14. US Food and Drug Administration, Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations. 2003; 1:1-23.
15. European Medicines Agency, Guideline on the Investigation of Bioequivalence. 2010; 1:1-27.
Published
Abstract Display: 527 
PDF Downloads: 1183 
