Relative bioavailability study with two oral formulations of topiramate using a validated UPLC-MS/MS method.
Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel and Topamax), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate were measured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC(0-inf) 63,418.31 +/- 22,141.69 and 67,094.70 +/- 22,487.2 ngh/ml; AUC0-24: 30,421.02 +/- 9,964.0 and 30,489.35 +/- 9,407.17, ng x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 2,143.33 +/- 724.26 and 2,262.51 +/- 751.12 ng/ml, for A (Toprel) and B (Topamax), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC(0-24) and AUC(0-inf) parameters are found within the range of 0.8 - 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax 100 mg, B (Reference).
Saavedra
I
I
Laboratory of Pharmacokinetics and Bioavailability, IFT, Molecular and Clinical Pharmacology Program, Biomedical Sciences Institute, Faculty of Medicine, University of Chile, Santiago, Chile.
Tamayo
E
E
Gamboa
A
A
Sasso
J
J
Varela
N
N
Moreno
I
I
Marchant
D
D
Cáceres
D
D
Quiñones
L
L
D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016568:Drugs, Generic / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D000077236:Topiramate; D055815:Young Adult
D000927:Anticonvulsants; D016568:Drugs, Generic; D013607:Tablets; D000077236:Topiramate; D005632:Fructose