Review of methods and criteria for the evaluation of bioequivalence studies

Pabst, G; Jaeger, H

doi:10.1007/bf00314794

Cited by 63 publications

(32 citation statements)

References 18 publications

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“…The variance associated with the pharmacokinetic parameters increases as their mean value increases. Therefore, a log transformation was applied to the data in order to satisfy the constant variance assumption for the analysis of variance [8]. All statistical tests were carried out at the 5% level of significance and comparisons were made with respect to the group of extensive metabolisers.…”

Section: Methodsmentioning

confidence: 99%

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

Ashforth¹,

Palmer²,

Bye³

et al. 1994

Brit J Clinical Pharma

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The pharmacokinetics of the 5-HT3 receptor antagonist ondansetron following an 8 mg i.v. dose were investigated in 12 subjects previously phenotyped with debrisoquine. Six subjects were poor metabolisers (debrisoquine metabolic ratios 29-131) and six were extensive metabolisers (debrisoquine metabolic ratios 0.45-3.4). There was no significant difference in AUC, Cmax, CL or t/2 between the poor and extensive metabolisers. It is concluded that ondansetron clearance is not mediated exclusively by cytochrome P-450 2D6.

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Section: Methodsmentioning

confidence: 99%

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

Ashforth¹,

Palmer²,

Bye³

et al. 1994

Brit J Clinical Pharma

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“…dose in the thigh region. According to (Pabst and Jaeger 1990), sampling continued for 3-5 biological half-lives in order to obtain correct pharmacokinetic parameters from plasma-concentration (C-T) curves. FivemL lithium heparinised vacutainer tubes and 22-G disposable needles were used for collection of 2 mL of blood at each bleeding point at the following intervals: 0.083, 0.167, 0.25, 0.5, 1, 2, 4, 8 and 12 (Phase-I); and at 0.25, 0.5, 1, 2, 4, 8 and 12 (Phase-II).…”

Section: Drug Administration and Blood Samplingmentioning

confidence: 99%

Pharmacokinetics of Lornoxicam in rabbits after single intravenous bolus and intramuscular administrations

El-Mahmoudy

2016

IJPT

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The pharmacokinetics of lornoxicam (a non-steroidal anti-inflammatory drug) at a dose of 0.4 mg/Kg body weight was evaluated after single intravenous (i.v.) and intramuscular (i.m.) bolus administrations in rabbits. An HPLC assay using pure lornoxicam base as a standard was used to measure its concentrations in plasma at prefixed time points up to 12 hours post administration. Following an i.v. bolus injection, the plasma concentration-time curves of lornoxicam were best represented by two-compartment open model. The drug was rapidly distributed and moderately eliminated with half-lives of distribution (t 1/2α ) and elimination (t 1/2β ) of 0.238 and 2.611 h, respectively. The volume of distribution was large with (V dss ) value of 1.499 L. The total body clearance (Cl B ) was 0.413 L/h. After i.m. bolus administration of the same dose, lornoxicam was moderately and completely absorbed in rabbits with an absorption half-life (t ½ab ) of 1.228 h with peak plasma concentration (C max ) of 0.463 μg/mL attained at 1.512 h (T max ) and systemic bioavailability of 99.79%. The elimination half-life following i.m. administration was 2.283 h. The extent of plasma protein binding percent was 98.9%. The study recommends the use of lornoxicam in rabbits because of its good pharmacokinetic profile indicated by good absorption, bioavailability and plasma concentrations.

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“…In this case, the occurrence of product effect indicates that there is a statistically significant difference between bioavailabilities of test and reference products regarding extension of drug absorption, but there is no difference regarding absorption rate, since no product effect was observed for C max . This difference in extension of drug absorption is not considered to be clinically important, since 90% CI is within the limits established by regulatory agencies (Pabst, Jaeger, 1990;Westlake, 1979). A period effect measures the differences between study periods.…”

Section: Discussionmentioning

confidence: 99%

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Kano

Koono

Schramm

et al. 2015

Braz. J. Pharm. Sci.

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Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic © (SanofiAventis Farmacêutica Ltda, Brazil, reference product) and Levaquin © (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters C max , T max , K el , T 1/2el , AUC 0-t and AUC 0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of C max , AUC 0-t and AUC 0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for C max , AUC 0-t and AUC 0-inf were 92.1% -108.2%, 90.7% -98.0%, and 94.8% -100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic © and Levaquin © are bioequivalent, since 90% CIs are within the 80% -125% interval proposed by regulatory agencies. A bioequivalência média de duas formulações de levofloxacino disponíveis no Brasil, Tavanic © (SanofiAventis Farmacêutica Ltda, Brasil, produto referência) e Levaquin © (Janssen-Cilag Farmacêutica Ltda, Brasil, produto teste) foi determinada por meio da realização de ensaio aleatório, aberto, cruzado, com dois períodos e duas sequências, em 26 voluntários sadios em condições de jejum. Amostras de sangue dos voluntários foram obtidas ao longo de um período de 48 horas após administração de dose única de 500 mg de levofloxacino. As concentrações plasmáticas do fármaco foram determinadas por método cromatográfico validado. Os parâmetros farmacocinéticos C max , T max , K el , T 1/2el , AUC 0-t e AUC 0-inf foram calculados por análise não compartimental. A bioequivalência foi determinada pelo cálculo de intervalos de confiança 90% (IC 90%) para as razões entre os valores de C max , AUC 0-t e AUC 0-inf obtidos para os produtos teste e referência, usando dados transformados logaritmicamente. A tolerabilidade foi avaliada pelo acompanhamento dos sinais vitais e resultados de exames laboratoriais, por consultas e por relato espontâneo dos voluntários. ICs 90% para C max , AUC 0-t e AUC 0-inf foram 92.1% -108.2%, 90.7% -98.0%, e 94.8% -100.0%, respectivamente. Os eventos adversos observados foram náusea e cefaleia. Concluiuse que os produtos Tavanic © e Levaquin © são bioequivalentes, uma vez que os ICs 90% estão dentro da faixa de 80%-125% proposta pelas agências reguladoras.Unitermos: Levofloxacino/bioequivalência. Farmacocinética. Cromatografia líquida de alta eficiência/ análise qualitativa. Tavanic

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Review of methods and criteria for the evaluation of bioequivalence studies

Cited by 63 publications

References 18 publications

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

Pharmacokinetics of Lornoxicam in rabbits after single intravenous bolus and intramuscular administrations

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

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