Category Archives: Pharmacokinetics

El farmacéutico clínico en el manejo farmacoterapéutico

J Pharm Pharmacogn Res 6(4): 285-298, 2018.

Original Article | Artículo Original

Impacto de la labor del farmacéutico clínico en el manejo farmacoterapéutico del paciente crítico: Experiencia local en un hospital docente asistencial

[Impact on the work of clinical pharmacist at the pharmacotherapy management of critically ill patient: Local experience in a clinical hospital]

Jorge S. Amador1*, Ruben A. Hernández1, Cristian M. Gutiérrez1, José C. Plaza-Plaza2

1Unidad de Pacientes Críticosítico Adulto, Hospital Clínico San Borja Arriarán, Santa Rosa 1234, Stgo. Centro. Santiago, Chile.
2Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile. Av. Vicuña Mackenna 4860. Macul. Santiago, Chile.

*E-mail: jamador@uc.cl

Abstract

Context: The complexity in critical patient management and polypharmacy, raise the need for support from a clinical pharmacist to optimize drug therapies.

Aims: To evaluate the clinical pharmacist participation in an Adult Intensive Care Unit in a local context where the practice is not well established.

Methods: The study was conducted in a teaching hospital. Consisted of two stages a retrospective in which were collected of pharmacotherapy follow-up during a period of two years and a prospective phase of observational and cross-sectional character, which picked up the clinical history of patients and pharmaceutical interventions. These pharmaceutical interventions were evaluated by two intensive care physicians and two external pharmacist, using a default score to each one of these, the degree of concordance was obtained using the kappa coefficient.

Results: In the retrospective phase were collected 182 patients, who were performed a total of 750 interventions, of which 99.7% was accepted by physician. In the prospective phase, were analyzed 53 patients that involved 263 pharmaceutical interventions with 96.6% of acceptance on the part of the medical staff. The degree of correlation of the interventions was κ = 0.61 between two physicians of the unit, and κ = 0.71 between two external pharmacists.

Conclusions: The contribution that a clinical pharmacist can provide in an adult intensive care has a positive impact on the treatment of patients with a high percentage of acceptances on the part of the medical team.

Keywords: critically ill patients; clinical pharmacist; pharmaceutical interventions.

Resumen

Contexto: La complejidad en el manejo del paciente crítico y la polifarmacia ha llevado a plantear la necesidad del apoyo por parte de un farmacéutico clínico para optimizar las terapias farmacológicas.

Objetivos: Evaluar la participación del farmacéutico clínico en una Unidad de Cuidados Intensivos (UCI) adulta.

Métodos: El estudio fue llevado a cabo en un hospital docente asistencial, y consistió en dos etapas; una retrospectiva en la cual se recopilaron fichas de seguimiento farmacoterapéutico durante dos años y una etapa prospectiva de carácter observacional transversal, en la cual se recopiló la historia clínica de los pacientes y las intervenciones farmacéuticas realizadas. Éstas fueron evaluadas por dos médicos intensivistas y dos químicos farmacéuticos externos, el grado de concordancia se obtuvo utilizando el coeficiente kappa.

Resultados: En la etapa retrospectiva se recopilaron las fichas de 182 pacientes, con un total de 750 intervenciones, de las cuales el 99,7% fue aceptado por los médicos. En la etapa prospectiva se analizaron 53 fichas con 263 intervenciones y 96,6% de aceptación por parte del equipo médico. El grado de correlación de las intervenciones fue de κ = 0,61 entre dos médicos de la unidad, y κ = 0,71 entre dos químicos farmacéuticos externos.

Conclusiones: El aporte que un químico farmacéutico puede brindar en una UCI adulta tiene un impacto positivo en el tratamiento de los pacientes, con un alto porcentaje de aceptación por parte del equipo médico.

Palabras Clave: farmacéutico clínico; intervención farmacéutica; paciente crítico.

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Citation Format: Amador JS, Hernández RA, Gutiérrez CM, Plaza-Plaza JC (2018) Impacto de la labor del farmacéutico clínico en el manejo farmacoterapéutico del paciente crítico: Experiencia local en un hospital docente asistencial [Impact on the work of clinical pharmacist at the pharmacotherapy management of critically ill patient: Local experience in a clinical hospital]. J Pharm Pharmacogn Res 6(4): 285–298.

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

RBC partitioning of cryptolepine

J Pharm Pharmacogn Res 6(4): 260-270, 2018.

Original Article | Artículo Original

Detection, quantification, and investigation of the red blood cell partitioning of cryptolepine hydrochloride

[Detección, cuantificación e investigación del reparto de clorhidrato de criptolepina en glóbulos rojos]

Regina A. Kwakye, Noble Kuntworbe*, Kwabena Ofori-Kwakye, Yaa A. Osei

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, PV Obeng Avenue, Tackie Building, PMB, Kumasi, Ghana.

*E-mail: nkunstar@yahoo.co.uk

Abstract

Context: The fight against malaria is limited by the development of resistance of Plasmodium to medication. This has led to an urgent search for alternative medicinal agents.

Aims: To determine the affinity of cryptolepine for the red blood cell.

Methods: HPLC method for the identification and quantification of cryptolepine was developed. Lipid solubility for both quinine (control) and cryptolepine was determined. Partitioning and repartitioning of cryptolepine into RBCs were studied. Time, concentration, temperature and pH were varied to see their effect on the partitioning of cryptolepine. Plasma protein binding was determined by the red blood cell partitioning method.

Results: An accurate, precise and robust HPLC method for cryptolepine hydrochloride was developed. Cryptolepine and quinine had lipophilicity of 0.91 ± 0.02 and 1.52 ± 0.27, respectively. The highest partitioning values of 2.02 ± 0.08 for cryptolepine and 0.93 ± 0.02 for quinine were obtained at 40 minutes. Concentration-dependent protein binding was observed for both compounds with cryptolepine having 0.43 and 0.38 for quinine. Partitioning was also found to be temperature dependent with the highest partitioning obtained at 370C for cryptolepine (1.56 ± 0.04) and quinine (0.78 ± 0.01). Partitioning of cryptolepine and quinine were inversely related to pH with R2 values of 0.94 and 0.96, respectively. P-values between partitioning and repartitioning for cryptolepine and quinine were 0.04 and 0.05, respectively.

Conclusions: Partitioning was found to be time, temperature, concentration and pH dependent. Partitioning was irreversible for cryptolepine and reversible for quinine. Protein binding in both cases was moderate.

Keywords: 4-aminoquinolone; erythrocyte; ion-trapping; quinine; repartitioning.

Resumen

Contexto: La lucha contra el paludismo está limitada por el desarrollo de la resistencia del Plasmodium a los medicamentos. Esto ha llevado a una urgente búsqueda de agentes medicinales alternativos.

Objetivos: Determinar la afinidad de la criptolepina para glóbulos rojos.

Métodos: Se desarrolló el método de HPLC para la identificación y cuantificación de criptolepina. Se determinó la solubilidad en lípidos tanto para la quinina (control) como para la criptolepina. Se estudió la división y repartición de la criptolepina en los glóbulos rojos. El tiempo, la concentración, la temperatura y el pH se variaron para ver su efecto en la partición de la criptolepina. La unión a proteínas plasmáticas se determinó mediante el método de división de glóbulos rojos.

Resultados: Se desarrolló un método HPLC exacto, preciso y robusto para el hidrocloruro de criptolepina. La criptolepina y la quinina tuvieron lipofilicidad de 0,91 ± 0,02 y 1,52 ± 0,27, respectivamente. Los valores de partición más altos de 2,02 ± 0,08 para criptolepina y 0,93 ± 0,02 para quinina se obtuvieron a los 40 minutos. Se observó unión a proteínas dependiente de la concentración para ambos compuestos con criptolepina 0,43 y 0,38 para quinina. El reparto también se encontró que dependía de la temperatura con la partición más alta obtenida a 37°C para la criptolepina (1,56 ± 0,04) y la quinina (0,78 ± 0,01). La división de la criptolepina y la quinina se relacionó inversamente con el pH con valores de R2 de 0,94 y 0,96, respectivamente. Los valores p entre partición y reparticionado para criptolepina y quinina fueron de 0.04 y 0.05, respectivamente.

Conclusiones: Se encontró que la partición depende del tiempo, la temperatura, la concentración y el pH. La partición fue irreversible para criptolepina y reversible para quinina. La unión a proteínas en ambos casos fue moderada.

Palabras Clave: 4-aminoquinolona; atrapamiento de iones; eritrocito; quinina; reparto.

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Citation Format: Kwakye RA, Kuntworbe N, Ofori-Kwakye K, Osei YA (2018) Detection, quantification, and investigation of the red blood cell partitioning of cryptolepine hydrochloride. J Pharm Pharmacogn Res 6(4): 260–270.

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Pharmacokinetics and pharmacodynamics of two novel PEGylated rHuEPO

J Pharm Pharmacogn Res 6(3): 179-190, 2018.

Original Article | Artículo Original

A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM

[Estudio comparativo farmacocinético y farmacodinámico de dos nuevas rHuEPO PEGiladas cubanas versus ior®EPOCIM y MIRCERA®]

Gledys Reynaldo1*, Leyanis Rodríguez1, Roberto Menéndez2, Joaquín Solazábal3, Daniel Amaro3, María de los A. Becquer4, Yamila Colom5, Haydee Gil5, Juan C. Polo1, Gilberto Castañeda6, Braulio Jiménez-Vélez7, Jorge Duconge8, Eduardo M. Fernández-Sánchez1,4

1Department of Pharmacy, Institute of Pharmacy & Foods, University of Havana, 222 St. and 23 Av. La Coronela, La Lisa, 13600, Havana, Cuba.
2Center of Neurosciences of Cuba, 190 St between 25 and 27, Cubanacan, Playa, 11600, Havana, Cuba.
3Center of Molecular Immunology, 216 St. and 15 St. Atabey, Playa. 11600, Havana, Cuba.
4Center for Research and Biological Evaluation, Institute of Pharmacy & Foods, University of Havana, 222 St. and 23 Av. La Coronela, La Lisa, 13600, Havana, Cuba.
5National Institute of Oncology and Radiobiology (INOR), 29 St. and F, Vedado, Plaza de la Revolución, 10400, Havana, Cuba.
6Department of Pharmacology, CINVESTAV-IPN, Av. IPN N0. 2508, Col. San Pedro Zacatenco, 07360, Delegación Gustavo A Madero, Mexico City, Mexico.
7University of Puerto Rico Medical Sciences Campus, Department of Biochemistry, School of Medicine, PO Box 365067, 00936-5067, San Juan, Puerto Rico.
8University of Puerto Rico Medical Sciences Campus, Department of Pharmaceutical Sciences, School of Pharmacy, PO Box 365067, 00936-5067, San Juan, Puerto Rico.

*E-mail: gledysrf@ifal.uh.cu

Abstract

Context: The recombinant human erythropoietin (rHuEPO) stimulates the erythropoiesis process. Because this glycoprotein has a short half-life, it needs to be administrated two to three times a week. One of the technics to solve this issue is the PEGgilation.

Aims: To evaluate the pharmacokinetics (PK) and pharmacodynamics of two new branched PEGylated erythropoietins (i.e., an asymmetric 32 kDa-PEG2-rHuEPO and a symmetric 40 kDa-PEG2-rHuEPO molecule) compared to non-PEGylated ior®EPOCIM and MIRCERA®.

Methods: Serum concentrations of both PEGylated and non-PEGylated erythropoietins were measured at various time points in order to determine PK parameters using non-compartmental analysis approach. The reticulocyte (%), erythrocyte count and hemoglobin levels were ascertained in order to compare the effect of these molecules after administrating a single intravenous dose (10 μg/kg) of each product in male New Zealand rabbits.

Results: Both branched PEGylated erythropoietin forms exhibited half-lives that were significantly longer than ior®EPOCIM (p<0.05), but not statistically different to MIRCERA®. The mean elimination half-life increased from 4 h (ior®EPOCIM) to 131 h for the 32 kDa-PEG2-rHuEPO and 119 h for the 40 kDa-PEG2-rHuEPO. Conversely, MIRCERA® exhibits a half-life of 64 h. Both PEGylated erythropoietin products significantly enhanced the stimulating effect on reticulocytes and erythrocytes formation, as well as on hemoglobin levels, when compared to ior®EPOCIM treatment up to 42 days post-dose.

Conclusions: The PEGylation strategy employed in this study is an effective method to modify the pharmacokinetics and pharmacodynamics of rHuEPO molecule achieving higher half-lives and, therefore, longer in vivo bioactivity. Both of the branched PEGylated-EPO forms tested are promising candidates for human testing.

Keywords: erythropoietin; non-compartmental analysis; PEGylated EPO; pharmacodynamics; pharmacokinetics; reticulocytes.

Resumen

Contexto: La eritropoyetina humana recombinante (rHuEPO) estimula la formación de eritrocitos en la medula ósea. Esta glicoproteína terapéutica presenta rápida eliminación en el organismo. Una de las estrategias tecnológicas para resolver esta problemática es la PEGgilación.

Objetivos: Evaluar la farmacocinética y la farmacodinámica de dos nuevas eritropoyetinas PEGiladas ramificadas (una asimétrica de 32 kDa-PEG2-rHuEPO y otra simétrica de 40 kDa-PEG2-rHuEPO) en comparación con ior®EPOCIM y el producto de referencia MIRCERA®.

Métodos: Se midieron las concentraciones séricas de eritropoyetina PEGilada y no PEGilada, a diferentes tiempos, para determinar los parámetros farmacocinéticos usando el método de análisis no compartimental. Se determinaron los % de reticulocitos, los niveles de eritrocitos y hemoglobina para comparar el efecto de estas moléculas después de administrar a dosis única 10 μg/kg por vía intravenosa en conejos Nueva Zelanda machos.

Resultados: Las eritropoyetinas PEGiladas ramificadas presentaron semividas significativamente superiores a ior®EPOCIM (p<0,05), pero no fueron estadísticamente diferentes a MIRCERA®. El t1/2 aumentó de 4 h (ior®EPOCIM) a 131 h para la 32 kDa-PEG2-rHuEPO y 119 h para la 40 kDa-PEG2-rHuEPO, respectivamente. Ambas eritropoyetinas PEGiladas mejoraron significativamente el efecto estimulante sobre la formación de reticulocitos y eritrocitos, así como los niveles de hemoglobina, en comparación con ior®EPOCIM hasta 42 días después de la dosis.

Conclusiones: La estrategia de PEGilación, empleada en este estudio, es un método efectivo para modificar la farmacocinética y farmacodinamia de moléculas de eritropoyetinas. Esta tecnología permitió aumentar la semivida de estas moléculas, así como prolongar su bioactividad in vivo. Ambas formas ramificadas de rHuEPO PEGiladas son candidatos prometedores para su uso clínico.

Palabras Clave: análisis no compartimental; eritropoyetina; eritropoyetina PEGilada; farmacocinética; farmacodinámica; reticulocitos.

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Citation Format: Reynaldo G, Rodríguez L, Menéndez R, Solazabal J, Amaro D, Becquer MA, Colom Y, Gil H, Polo JC, Castañeda G, Jiménez-Vélez B, Duconge J, Fernández-Sánchez EM (2018) A comparative pharmacokinetic and pharmacodynamic study of two novel Cuban PEGylated rHuEPO versus MIRCERA® and ior®EPOCIM. J Pharm Pharmacogn Res 6(3): 179–190.

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Comparison of artemether-lumefantrine formulations

J Pharm Pharmacogn Res 6(3): 167-178, 2018.

Original Article | Artículo Original

Comparison of the physicochemical properties and in vivo bioavailability of generic and innovator artemether-lumefantrin tablets in Kumasi, Ghana

[Comparación de las propiedades fisicoquímicas y la biodisponibilidad in vivo de comprimidos genéricos e innovadores arteméter-lumefantrina en Kumasi, Ghana]

Noble Kuntworbe*, Francis A. Acquah, Raphael Johnson, Kwabena Ofori-Kwakye

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, PV Obeng Avenue, Tackie Building, PMB, Kumasi, Ghana.

*E-mail: nkuntworbe.pharm@knust.edu.gh, nkunstar@yahoo.co.uk

Abstract

Context: Malarial remains a leading course of death in developing countries. Current treatment protocol involves the use of artemisinin-based combination therapy. In endemic areas, cost of treatment is a concern hence generic prescription is on the high. It is therefore necessary to investigate how equivalent or otherwise the generics are to the innovator brand Coatem®.

Aims: To compare the physicochemical properties and in vivo bioavailability of a locally manufactured generic artemether-lumefantrine tablet formulation and that of the innovator brand sold on the Kumasi market, Ghana.

Methods: The most used locally manufactured generic and the innovator brands were sampled from retail pharmacies. The samples were confirmed by colorimetry. Pharmaceutical equivalence of the brands was determined using compendial tests. In vivo bioavailability study on the two brands was done using a two-period, single dose, cross-over design involving 20 healthy rabbits. Pharmacokinetic parameters (AUC0-72, AUC0-∞, and Cmax) for both brands derived from the study were analysed statistically.

Results: Both the generic and innovator brands passed the physicochemical tests. The artemether component of both brands complied with the pharmacopoeia specification for dissolution testing while the lumefantrine did not. Average bioequivalence was demonstrated per the FDA criterion with the geometric mean ratios and corresponding 90% confidence intervals falling within the acceptable limits of 0.80 – 1.25.

Conclusions: Based on the similarity demonstrated between the two brands, evidence have been shown to support substitutability of the often-expensive innovator brand with the affordable locally produced brand.

Keywords: artemether-lumefantrine; bioequivalence generic-substitution; pharmacokinetics.

Resumen

Contexto: La malaria sigue siendo una causa principal de muerte en los países en desarrollo. El protocolo de tratamiento actual implica el uso de terapia de combinación basada en la artemisinina. En áreas endémicas, el costo del tratamiento es una preocupación y la prescripción genérica está auge. Por lo tanto, es necesario investigar qué tan equivalentes o genéricos son los medicamentos para la marca innovadora Coatem®.

Objetivos: Comparar las propiedades fisicoquímicas y la biodisponibilidad in vivo de una formulación de tableta de artemeter-lumefantrina genérica, fabricada localmente, y la de la marca innovadora vendida en el mercado de Kumasi, Ghana.

Métodos: Se tomaron muestras de las marcas genéricas e innovadoras más utilizadas en las farmacias minoristas. Las muestras fueron confirmadas por colorimetría. La equivalencia farmacéutica de las marcas se determinó mediante pruebas compendiales. El estudio de biodisponibilidad in vivo en las dos marcas se realizó utilizando un diseño cruzado de dosis única de dos períodos en el se utilizaron 20 conejos sanos. Los parámetros farmacocinéticos (AUC0-72, AUC0-∞ y Cmax), para ambas marcas derivadas del estudio, se compararon estadísticamente.

Resultados: Tanto las marcas genéricas como innovadoras pasaron las pruebas fisicoquímicas. El componente de arteméter de ambas marcas cumplió con la especificación de la farmacopea para las pruebas de disolución, mientras que la lumefantrina no lo hizo. La bioequivalencia promedio se demostró según el criterio de la FDA con las razones de medias geométricas y los correspondientes intervalos de confianza del 90% dentro de los límites aceptables de 0,80 a 1,25.

Conclusiones: En base a la similitud demostrada entre las dos marcas, se ha demostrado que las pruebas respaldan la sustitución de la marca innovadora, a menudo cara, con la marca de producción local asequible.

Palabras Clave: arteméter-lumefantrina; farmacocinética; sustitución genérica de bioequivalencia.

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Citation Format: Kuntworbe N, Acquah FA, Johnson R, Ofori-Kwakye K (2018) Comparison of the physicochemical properties and in vivo bioavailability of generic and innovator artemether-lumefantrin tablets in Kumasi, Ghana. J Pharm Pharmacogn Res 6(3): 167–178.

© 2018 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS OF TWO FORMULATIONS CONTAINING SYNERGISTIC PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA IN HEALTHY MALE VOLUNTEERS (SOFIA STUDY)

J Pharm Pharmacogn Res 2(Suppl. 1): S9, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS OF TWO FORMULATIONS CONTAINING SYNERGISTIC PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA IN HEALTHY MALE VOLUNTEERS (SOFIA STUDY)

García I1, Díaz A2, Tuero AD1, González CA2, Pérez S2, García Y1, Campos R1, Valenzuela CM1, Cruz A1, Cervantes M1, Martín A2, Vásquez DM3, Howland I4, Bello I1.

1Clinical Investigation Department, Center for Genetic Engineering and Biotechnology (CIGB), Ave 134 e/ 23 and 25, Cubanacán, Playa, P.O. Box 6332, Havana 10600, Cuba. Telephone: +53 (7) 2087379; 2087465; Fax: +53 (7) 2736008. Email: idrian.garcia@cigb.edu.cu
2National Center for Toxicology, “Carlos J. Finlay” University Hospital, Ave. 31 and 114, Marianao, Havana 11400, Cuba.
3Genomics Department, CIGB, Ave 134 e/ 23 and 25, Cubanacán, Playa, Havana 10600, Cuba.
4Clinical Laboratory, Center for Medical-Surgical Research, 216 and 11-B, Siboney, Playa, Havana 10600, Cuba.
Abstract

Introduction: A sustained full Interferon (IFN)-receptor interactions with more potent antiproliferative activity are desired in the treatment of cancer. This is possible to obtain combining IFN-alpha and IFNgamma that synergize for their biological activities.

The aim of this study was to characterize pharmacodynamics, pharmacokinetics and biological safety of two formulations (CIGB-128 and CIGB-128-A) based on the combination of IFNs alpha-2b and gamma in healthy male volunteers.

Material and methods: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 24.5 x 106 IU IFN mixture dose was administered intramuscularly. Thirteen apparently healthy male subjects were included. Classical IFN-inducible serum markers, neopterin, beta2-microglobulin (β2M), and 2’-5’ oligoadenylate synthetase (2′-5′ OAS), were used as indicators of their pharmacodynamic action. Serum IFN concentration was measured during 48 hours by enzyme immunoassay. Adverse events were rigorously checked.

Results: Neopterin levels at 24-48 hours post-administration were 9 times superior to the initials. This high increment has not been described before in the literature with any subtype or variant of IFN. At the same time mean serum β2M peaked around the double from baseline. The concentrations of the enzyme 2′-5′ OAS were still elevated at the eighth day post-injection. Concerning pharmacokinetics, no interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles; parameters as Tmax (7-10 hours) and t1/2 (6 hours) were within the reported ranges for these conventional IFNs. Both products were well tolerated. The most frequent adverse reactions were fever, headache, arthralgias and lymphopenia, mostly mild. Serum IFN concentrations has a direct, strong correlation with body temperature.

Conclusions: The potent synergistic IFN mixture possesses improved pharmacodynamic properties without additional toxicity that may useful in the oncologic setting leading to less frequent injections, and a better patient’s compliance and quality of life.

C 005: PHARMACOKINETIC CHANGES INDUCED BY SPINAL CORD INJURY

J Pharm Pharmacogn Res 2(Suppl. 1): S21, 2014

Special supplement with the abstract book of LATINFARMA 2013

Conference

C 005: PHARMACOKINETIC CHANGES INDUCED BY SPINAL CORD INJURY

Castañeda G.

Departamento de Farmacología. Centro de investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Av. Instituto Politécnico Nacional 2508, 07360 México, D.F.
Abstract

Spinal cord injury (SCI) is a life-threatening event that not only results in a sensory-motor loss below the site of lesion, but also causes autonomic alterations including gastrointestinal and hemodynamic changes. These changes are known to modify drug availability. Significant changes in drug absorption, volume of distribution and clearance have been reported in patients after cord lesion and it has been suggested that these changes could have an impact on the efficacy and safety of a variety of drugs in this population. Characterization of the physiopathological alterations underlying pharmacokinetic changes that occur in patients with SCI has been complicated because of the important variability induced by differences in injury characteristics, as well as in the individual conditions of each patient. Moreover, not all drugs exhibit altered disposition after SCI. Therefore, depending on which physiological mechanisms are involved in the absorption, distribution and elimination of a given drug, SCI will or will not change its pharmacokinetic parameters. There is evidence suggesting that the magnitude of the pharmacokinetic changes will depend on variables related to the injury itself: site of injury, intensity and the time elapsed after lesion. However, at present we do not have enough information to propose a rational strategy for drug dosing in patients with spinal cord injury. Doses are selected on empirical bases, often resulting in therapeutic failure. Thus, systematic research is required to fully elucidate this issue. Hence, our group has used animal models, where the lesion can be standardized, to characterize and understand the impact of spinal cord injury on drug disposition.