Estudos de bioequivalencia de duas formulações comerciais de Nimodipina e Ambodipina

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

Objectíve: This thesis had as objective to evaluate the bioequivalence through the pharmacokinetic and pharmacodynamic of two comercial formulations of two Calcium Blockers, Amlodipine (Biosintética CordareneR tablets 5 mg vs Pfizer NorvascR tablets 5 mg) and Nimodipine (Biosintética OxigenR tablets 90 mg vs Bayer NimotopR tablets 90 mg). It was selected thirty seven (37) volunteers, male, between 18 and 45 years old, healthy, to randomized study, not blind, and divided in two groups (Group Amlodipine [19 vol.] and Group Nimodipine [18 vol.]). Blood samples of volunteers were collected according to pre stabilished time. After determination of the plasmatic levels of the medicine in question, it was realized pharmacokinetic analysis obtaining the maximum plasmatic concentration (Cma0 and the time obtained to reach this maximum levei (T max). The areas under the time curves vs concentration of Amlodipine (AUC[0-144h]) e Nimodipine (AUC[O24h]) , in separate, they were calculated utilizing the trapezoidal method. The constant of terminal elimination of first order (Ke) of the drugs Amlodipine and Nimodipine were determinated from of the equation of linear regression between the logarithmic of concentration and the time. The half lives (T 1/2) were calculated applying the equation T1/2= (In2/Ke). Results: In this study there wasn t significant variation of the blood pressure and heart rate with administration of a single dQse of the formulations of the studied drugs. The Areas Under the Curve of Amlodipine drugs (AUC[0-144h]) were compared. Biosintética Amlodipine AUC[0-144h] arithmetic mean ratio was 94.23% of Pfizer Amlodipine (Westlake s 90% confidence interval 90.1-109.9%). Biosintética Amlodipine AUC[0-144h] geometric mean ratio was 93.69% of. Pfizer Amlodipine (Westlake s 90% confidence interval 89.8-110.2%) The maximum concentrations reached (Cma0 were also compared. Biosintética Amlodipine Cmax arithmetic mean ratio was 93.58% of Pfizer Amlodipine (Westlake s 90% confidence interval 88.1-111.9%). Biosintética Amlodipine Cmax geometric mean ratio was 93.49% of.. Pfizer Amlodipine (Westlake s 90% confidence interval 88.6-111.3%). The calculation were done following the logarithmic transformation and the ratio probability to be including within of the interval 0.8 - 1.25% was 1.0 and 1.0 respectively to AUC[G -144) and Cmax (two one sided t-Test). The Areas Under the Curve of Nimodipine drugs (AUC[G-24h]) were compared. Biosintética Nimodipine AUC[0-24h] arithmetic mean ratio was 94.5% of Bayer Nimodipine (Westlake s 90% confidence interval 74.0 - 126.0%). Biosintética Nimodipine AUC[G-24h] geometric mean ratio was 98.8% of. Bayer Nimodipine (Westlake s 90% confidence interval76.2 - 124.7%) The maximum concentrations reached (Cmax) were also compared. Biosintética Nimodipine Cmax arithmetic mean ratio was 95.3% of Bayer Nimodipine (Westlake s 90% confidence interval 70.7 - 129.3%). Biosintética Nimodipine Cmax geometric mean ratio was 107% of. Bayer Nimodipine (Westlake s 90% confidence interval62.9 - 137.0%). The calculation were done following the logarithmic transformation and the ratio probability to be including within of the interval 0.8 - 1.25% was 0.91 and 0.92 respectively to AUC[0-24) and Cmax (two one sided t-Test). Through of the mean ratio parameters of Ke and T1/2 from Amlodipine e Nimodipine, they showed significant differences. The Ke and T1/2 of Amlodipine were 0.01 h and 38.6 h respectively ~nd Nimodipine 0.54 h and 1.29 h Respectively. Conclusion: We concluded that the substitution of Bayer Nimodipine (Nimot9~)R) and Pfizer Amlodipine (NorvascR) for their equivalents Biosintética Nimodipine (OxigenR) and Biosintética Amlodipine (CordareneR) respectively is perfectly possible, once their absorption velocity and extension are within of the parameters required by FDA. In relation to kinetic comparetion of the Amlodipine and Nimodipine drugs that are originated from prototype of Nefidipine, Dihydropyridinic class, we conclude what the introduction of differents radicais in the its basic molecule is able to promote alteration in its phisical-chimestry property. In this way, the Amlodipine drug has a slow action begining, distribuition extensive and low metabolization when compared to Nimodipine drug

ASSUNTO(S)

farmacocinetica

ACESSO AO ARTIGO

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