Farmacogenómica: aplicaciones cardiovasculares / Pharmacogenomics: cardiovascular applications

Las enfermedades cardiovasculares constituyen un importante problema de salud pública al ser la principal causa de morbilidad y mortalidad en el mundo. Por ello, existe la creciente necesidad de tratamientos farmacoterapéuticos más eficaces y seguros. Sin embargo, a pesar de que los médicos prescriben fármacos sobre la base de las características farmacológicas del medicamento y la probabilidad de obtener resultados clínicamente reproducibles, muchos de los fármacos son eficaces sólo entre 25-60% de los pacientes. En este sentido es que la Farmacogenómica, a través del estudio de variantes genéticas de proteínas involucradas en la farmacocinética y farmacodinamia de los medicamentos, persigue maximizar su eficacia y seguridad, Este trabajo pretende dar una visión general acerca de farmacogenómica cardiovascular y la posibilidad de utilizar, en la consulta clínica, herramientas genéticas para apoyar la decisión farmacoterapéutica, con el objeto de mejorar la respuesta al tratamiento de enfermedades cardiovasculares, un paso hacia la medicina personalizada en Chile.

Cardiovascular disease is a major public health problem being the leading cause of morbidity and mortality worldwide. Therefore, there is a growing need for safer and more effective pharmacotherapeutic treatments. However, although physicians prescribe drugs based on pharmacological properties of each drug and the probability of obtaining clinically reproducible results, many drugs are effective only in 25-60% of patients. In this respect, pharmacogenomics, through the study of genetic variants of proteins involved in the pharmacokinetics and pharmacodynamics of drugs, pursues to maximize their efficacy and safety, This paper aims to give an overview of cardiovascular pharmacogenomics and the possibility to use, in clinical practice, genetic tools to support pharmacotherapeutical decisions, in order to improve the response to treatment of cardiovascular diseases, a step toward personalized medicine in Chile.

Postmarketing pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol in Egypt

Concerns have raised regarding the postmarketing quality of generic drugs. This study assessed the pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol tablets in 24 healthy male volunteers in a single-dose, open, randomized, two-period crossover study under fasting conditions. Blood samples were collected for 24 h post dosing and assayed for atenolol using HPLC. Blood pressure and heart rate were measured at baseline and throughout blood sampling. The mean plasma concentration-time curves for both products were similar. Pharmacokinetic and statistical analysis indicated bioequivalence based on the mean ratios of log-transformed Cmax and AUC values. Both products had similar time courses of pharmacodynamic activity with a significant fall in blood pressure and heart rate [maximum after 5 h] followed by a gradual increase towards baseline. Both products were well tolerated. Both atenolol products were bioequivalent in the postmarketing setting and can be used interchangeably in clinical practice

A preliminary study on pharmacokinetics of oral indomethacin in premature infants in north India.

BACKGROUND & OBJECTIVES: Patent ductus arteriosus (PDA) is a frequent complication in premature infants. Intravenous indomethacin is the standard mode of medical therapy and has been shown to be efficacious in closing the ductus. In our setup, oral indomethacin is being regularly used for medical treatment of suspected or clinically diagnosed PDA. Non-availability of the parenteral preparation and lack of information regarding the pharmacokinetic disposition of indomethacin in the premature infants in north Indian population led us to conduct this pharmacokinetic study with oral indomethacin. METHODS: Twenty premature infants with gestational age 30.3 +/- 0.3 wk and birth weight, 1209.8 +/- 39.5 g; admitted to the neonatal unit of the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh were enrolled in the study. Indomethacin was administered in a single oral dose of 0.2 mg/kg and blood samples were collected through an indwelling vascular catheter at 0 and 1, 2, 4, 8 and 12 h after administration of indomethacin. Plasma indomethacin concentrations were assayed by spectrofluorometric technique. RESULTS: Large interindividual variability was observed for peak plasma concentrations (Cmax; 137.9 +/- 14.0 ng/ml), elimination half-life (t1/2 el; 21.4 +/- 1.7 h) and area under the plasma concentrations time curve (AUC0-infinity;4172 +/- 303 ng.h/ml) in these infants. Variables like birth weight, and sex did not have any sigiificant effect on indomethacin pharmacokinetics. However, the plasma t1/2 el of indomethacin was significantly (P < 0.01) larger in older infants (gestational age > 30 wk) in comparison to younger ones (gestational age < or = 30 wk). There was a negative correlation between gestational age and elimination t1/2 (r = -0.77). INTERPRETATION & CONCLUSION: In conclusion, indomethacin pharmacokinetics showed a wide variability in premature infants. In view of these findings it can be suggested that infants of smaller gestational age are at greater risk of cumulative toxicity if more than one dose of indomethacin is given. With advancing age, metabolism as well as elimination of drug is faster that may require modification in indomethacin dose to achieve therapeutic response. These preliminary results may be of use in designing future pharmacokinetic studies of oral indomethacin in preterm neonates on a larger sample.