ABSTRACT
Los informes de la evaluación cinética de los medicamentos desarrollados en los últimos 20 años documentan, prioritariamente, los resultados de ensayos realizados exclusivamente con varones; o bien, con muestras mixtas por cuyos resultados no se reagrupan ni analizan por la variable de sexo...
Subject(s)
Humans , Male , Female , Benzodiazepines/analysis , Benzodiazepines/pharmacokinetics , Lorazepam/analysis , Lorazepam/pharmacokinetics , Costa RicaABSTRACT
Two strains of rats, Sprague-Dawley and Wistar, were assayed in order to determine which strain is the more suitable experimental model for the study of pharmacokinetic alterations inuced by spinal cord injury. Animals were submitted to spinal cord contusion at the T8-T9 level by the weight drop method. A single acetaminophen oral dose (100 mg/kg) was administered 24 h after injury and blood samples were drawn for a period of 4 h. Acetaminophen concentration in whole blood was determined by high performance liquid chromatography and pharmacokinetic parameters were estimated. For both strains, Cmax and AUC were significantly lower, whereas tmax remained uchanged, in injured animals compared to sham-injured controls. Circulating acetaminophen concentrations were higher; therefore, pharmacokinetic alterations were more easily discerned, in Sprague-Dawley than in Wistar rats. It is concluded that the Sprague-Dawley strain is a more suitable model for the study of pharmacokinetic alternations induced by spinal cord injury
Subject(s)
Rats , Animals , Acetaminophen/pharmacokinetics , Amikacin/pharmacokinetics , Disease Models, Animal , Gentamicins/pharmacokinetics , Lorazepam/pharmacokinetics , Pharmacokinetics , Rats, Sprague-Dawley/cerebrospinal fluid , Rats, Wistar/cerebrospinal fluid , Theophylline/pharmacokinetics , Spinal Cord Injuries/complicationsABSTRACT
Differential scanning calorimetry [DSC] was mainly employed to predict the physicochemical incompatibility of 3 benzodiazepines, viz. temazepam, medazepam and lorazepam, with some common pharmaceutical excipients. The 3 drugs were found to be compatible with Avicel, Ac- Di-Sol, lactose, HPMC, dibasic calcium phosphate, starch, PVP and magnesium stearate. However, interactions of the benzodiazepines with PEG and stearic acid were detected and well confirmed utilizing TLC technique in addition to DSC