ABSTRACT
Background: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. Aim: To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex) compared to the reference formulation (Cellcept) to determine the bioequivalence between both formulations. Material and Methods: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. Results: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. Conclusions: Linfonex 500 mg is bioequivalent to Cellcept 500 mg.
Subject(s)
Adult , Humans , Male , Immunosuppressive Agents/pharmacokinetics , Mycophenolic Acid/analogs & derivatives , Administration, Oral , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Cross-Over Studies , Double-Blind Method , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/pharmacokinetics , Therapeutic EquivalencyABSTRACT
Cytochrome P450 enzymes are very important to metabolize anti-carcinogenic agents. Therefore, understanding the role of these enzymes and their allele variants in the bioactivation or detoxification of drugs could greatiy benefit antineoplastic pharmacotherapy. The aim of thís manuscrípt is to give information about metabohzing enzymes for antineoplastic agents and to relate the current situation in antitumoral pharmacotherapy with recent knowledge about cytochrome P450 enzymes. This is crucial for the future perspectives towards personalized pharmacotherapy. We summarize the role of cytochrome P450 enzymes in the resistance and bioactivation of several antitumor agents, their induction and repression mechanisms and the effect of genetic polymorphisms on variability of drug metabolization. The understanding of genetic variability will help to develop new research Unes on innovative therapeutic possibilities.
Subject(s)
Humans , Antineoplastic Agents/metabolism , /physiology , Neoplasms/metabolism , Polymorphism, Genetic , Antineoplastic Agents/therapeutic use , /antagonists & inhibitors , /genetics , Drug Interactions , Enzyme Induction/physiology , Enzyme Inhibitors/pharmacology , Neoplasms/drug therapyABSTRACT
Pharmacokinetics corresponds to the branch of pharmacology that studies the absorption, distribution, biotransformation and excretion of drugs in the body, in order to proportionate a reference line for interpretation of drug concentration in biological fluids, fundamental for clinical therapy. While adult pharmacology has increase greatly, advances in pediatric pharmacology have been poor. Therefore, drug prescription in children is essentially empirical on the basis of an inmature organism. An effective, secure and rational pediatric pharmacology requires exhaustive knowledgement of the developmental changes in relation to absorption, distribution, metabolism and excretion affecting pharmacokinetics parameters; therefore, the effective dose. This review describes fundamental differences between adult and pediatric pharmacokinetics. These differences must be considered when therapeutic strategies develop for newborns and children.
La farmacocinética, rama de la farmacología que estudia el paso de las drogas a través del organismo en función del tiempo y la dosis tiene por finalidad el proporcionar un marco de referencia para interpretar la concentración de los fármacos en los líquidos biológicos por el bien del paciente, lo que es fundamental para una correcta terapéutica clínica. Mientras los avances en farmacología clínica del adulto en las últimas décadas tuvieron un gran adelanto, no ha ocurrido lo mismo en farmacología pediátrica donde la mayoría de las veces la prescripción de medicamentos se realiza sobre una base empírica en un organismo inmaduro. Una terapéutica farmacológica efectiva, segura y racional en neonatos, lactantes y niños requiere el exhaustivo conocimiento de las diferencias en la absorción, distribución, metabolismo y excreción, las que aparecen durante el crecimiento y desarrollo, debido a que virtualmente, todos los parámetros farmacocinéticos se modifican con la edad. Esta revisión describe las diferencias fundamentales en la farmacocinética de los medicamentos en el niño cuando se compara con el adulto. Estas diferencias y los cambios en estos procesos deben ser cuidadosamente considerados cuando se desarrollan estrategias terapéuticas en recién nacidos y niños pequeños.