Bioequivalence evaluation of single doses of two tramadol formulations: A randomized, open-label, two-period

Silva, Marina de Freitas; Schramm, Simone Grigoleto; Kano, Eunice Kazue; Koono, Eunice Emiko Mori; Porta, Valentina; Serra, Cristina Helena dos Reis

doi:10.1016/j.clinthera.2010.03.016

Cited by 10 publications

(5 citation statements)

References 14 publications

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“…Sampling schedules enabled proper characterization of the pharmacokinetic profiles. Tramadol and O-desmethyltramadol pharmacokinetics reported in this paper are in line with literature data for achiral methods [23,24]. Pharmacokinetics in overweight subjects were similar to normal weight subjects, in line with observations of Porażka et al [36].…”

Section: Discussionsupporting

confidence: 92%

“…A different enantiomeric ratio for tramadol and its main metabolites has been observed after intravenous and oral administration [21] and some gender differences have also been reported [22]. The mean plasma elimination half-life in healthy subjects after a single-dose administration ranges from 4.7 to 7.9 h [23][24][25]. After multiple dosing (50 mg every 6 h), the plasma steady state is reached within 3 days [26].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

et al. 2021

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Background Magnesium ions (Mg2+) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg2+ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. Methods Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Both studies were randomized, open label, laboratory-blinded, two-period, two-treatment, crossover trials. The plasma concentrations of tramadol and its active metabolite, O-desmethyltramadol, were measured. Results A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively. Both primary and secondary pharmacokinetic parameters were similar. The 90% confidence intervals for Cmax and AUC0-t geometric mean ratios for tramadol were 91.95–102.40% and 93.22–102.76%. The 90% confidence intervals for Cmax,ss and AUC0-τ geometric mean ratios for tramadol were 93.85–103.31% and 99.04–105.27%. The 90% confidence intervals for primary pharmacokinetic parameters were within the acceptance range. ANOVA did not show any statistically significant contribution of the formulation factor (p > 0.05) in either study. Adverse events and clinical safety were similar in the presence and absence of Mg2+. Conclusions The absence of Mg2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain. Graphic abstract

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

et al. 2021

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“…Drug absorption is mainly assessed by bioavailability/ bioequivalence assays (24)(25)(26). However, such studies are subject to a number of sources of variation, for example, the individual variability (intra-individual and inter-individual); have a high cost; and involve healthy individuals, promoting discussion of comprehensive ethical issues of these tests (27,28).…”

Section: Gastrointestinal Physiology: Impact On Drug Deliverymentioning

confidence: 99%

Biomagnetic Methods: Technologies Applied to Pharmaceutical Research

et al. 2010

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Biomagnetic methods have been designed for a wide range of applications. Recently, such methods have been proposed as alternatives to scintigraphy for evaluating of a number of pharmaceutical processes in vitro as well as under the influence of gastrointestinal physiological parameters. In this review, physical characterization as well as the most recent applications of Superconducting Quantum Interference Device (SQUID), Anisotropic Magnetoresistive (AMR) and AC Biosusceptometry (ACB) in the pharmaceutical research will be explored. Moreover, their current status and how these technologies can be employed to improve the knowledge about the impact of gastrointestinal physiology on drug delivery in association with pharmacokinetic outcomes, termed pharmacomagnetography, will be presented.

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“…Drug products that are pharmaceutical equivalents are considered bioequivalent and, therefore, interchangeable when BA is not statistically different between the two products after administration at the same dose and under similar experimental conditions in a bioequivalence (BE) study. For purposes of establishing BE, a test product must be compared to a reference product [1,2,3].…”

Section: Introductionmentioning

confidence: 99%

In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation

et al. 2019

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A biowaiver is accepted by the Brazilian Health Surveillance Agency (ANVISA) for immediate-release solid oral products containing Biopharmaceutics Classification System (BCS) class I drugs showing rapid drug dissolution. This study aimed to simulate plasma concentrations of fluconazole capsules with different dissolution profiles and run population simulation to evaluate their bioequivalence. The dissolution profiles of two batches of the reference product Zoltec® 150 mg capsules, A1 and A2, and two batches of other products (B1 and B2; C1 and C2), as well as plasma concentration–time data of the reference product from the literature, were used for the simulations. Although products C1 and C2 had drug dissolutions < 85% in 30 min at 0.1 M HCl, simulation results demonstrated that these products would show the same in vivo performance as products A1, A2, B1, and B2. Population simulation results of the ln-transformed 90% confidence interval for the ratio of Cmax and AUC0–t values for all products were within the 80–125% interval, showing to be bioequivalent. Thus, even though the in vitro dissolution behavior of products C1 and C2 was not equivalent to a rapid dissolution profile, the computer simulations proved to be an important tool to show the possibility of bioequivalence for these products.

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Bioequivalence evaluation of single doses of two tramadol formulations: A randomized, open-label, two-period

Cited by 10 publications

References 14 publications

Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

Biomagnetic Methods: Technologies Applied to Pharmaceutical Research

In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation

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