RESUMEN
Individualizing drug dosage regimens is a common application of therapeutic drug monitoring. For drugs with a narrow therapeutic index or variable pharmacokinetic parameters, pharmacokinetic-based dosing can be useful. Pharmacokinetic methods that can aid the clinician in targeting for desired drug serum concentrations have been developed and clinically evaluated. These methods range from single nomograms or pharmacokinetic equations in which no serum concentrations are necessary to more complex techniques requiring serum concentration data and computer support. The most recently developed technique, Bayesian forecasting, may allow for more precise dosage individualization.
Asunto(s)
Preparaciones Farmacéuticas/administración & dosificación , Relación Dosis-Respuesta a Droga , Humanos , Monitoreo Fisiológico , Preparaciones Farmacéuticas/sangreRESUMEN
Although nifedipine is commonly administered sublingually in the clinical setting, a comparison of the serum concentrations obtained by this route vs oral administration has not been previously made. Nifedipine serum concentrations were measured in 6 healthy subjects following sublingual or oral administration of one nifedipine 10 mg capsule. Serum nifedipine concentrations were measured at regular intervals and demonstrated that sublingual administration produced measurable nifedipine concentrations sooner than oral administration. Peak nifedipine serum concentrations were less following sublingual administration (41.9 +/- 24.9 ng/ml) than following oral administration (99.6 +/- 49.8 ng/ml, p less than 0.05). The time to peak nifedipine serum concentration was also longer following sublingual administration than with the oral dose (74 +/- 24 minutes vs 40 +/- 14 minutes, p less than 0.05). Despite these differences, the areas under the serum concentration-time curve of the two routes of administration were similar. These differences in nifedipine concentrations may be an important consideration when choosing the route of administration of nifedipine.
Asunto(s)
Nifedipino/administración & dosificación , Administración Oral , Adulto , Femenino , Humanos , Cinética , Masculino , Suelo de la Boca , Nifedipino/sangre , Análisis de RegresiónRESUMEN
The derived pharmacokinetic variable estimates from a Bayesian aminoglycoside dosing program were compared with those from the Sawchuk-Zaske method to determine which variable estimates were the most accurate in fitting the test dose and in predicting subsequent peak and trough serum concentrations. Data on 17 patients with moderately impaired but stable renal function were analyzed. All patients received gentamicin sulfate for treatment of their infections. To determine the individualized variables using the Bayesian program, demographic data, dosing history, and one (midpoint), two (peak and trough), or four serum drug concentrations were entered into the program. The Sawchuk-Zaske method used three serum concentrations determined following a first dose or four concentrations before and after a subsequent dose to derive individualized pharmacokinetic variables. The estimates of pharmacokinetic variables determined using the Bayesian method with one, two, or four serum concentrations did not differ significantly from those obtained using all the available serum concentrations with the Sawchuk-Zaske method. Although the actual numeric differences of prediction, absolute, and squared errors for fitting the test dose were minimal, significant differences were seen. All methods were similar in predicting serum concentrations from continued dosing. For the prediction error from continued dosing, a slight but significant difference was observed with the Bayesian method using one serum concentration when compared with the other methods. The Bayesian method using one, two, or four serum gentamicin concentrations individualized pharmacokinetic variables as well as the Sawchuk-Zaske method.
Asunto(s)
Gentamicinas/administración & dosificación , Anciano , Teorema de Bayes , Gentamicinas/sangre , Humanos , Cinética , Persona de Mediana Edad , Modelos Biológicos , Programas InformáticosRESUMEN
Four methods of predicting serum gentamicin concentrations (SGCs) in adult patients with stable impaired renal function were compared. Serum samples obtained from 17 patients receiving intravenous gentamicin therapy were assayed for gentamicin using a radioimmunoassay. Kinetic variables derived using four different methods were used to predict peak and trough concentrations. The Sawchuk-Zaske method uses individualized apparent volume of distribution (Vapp) and half-life (t1/2) derived from at least three SGCs following a given dose. The fitted method assumes Vapp equals 0.28 liters/kg lean body weight (LBW) and a t1/2 derived by a fitting technique using only one SGC. Both the Tozer and Hull methods assume Vapp equals 0.28 liters/kg LBW, and t1/2 is estimated from equations that take into account the patient's renal function (creatinine clearance). The predicted and measured SGCs for each method were compared using linear regression analysis. The prediction errors, defined as the predicted minus the measured SGC, were compared for the four methods. The correlation coefficients between the measured and predicted SGCs were significant at p less than 0.05 only for the Sawchuk-Zaske and fitted methods. For the Sawchuk-Zaske method, peak and trough r values were 0.73 and 0.91, respectively. For the fitted method, peak and trough r values were 0.53 and 0.71, respectively. No significant differences in the mean prediction errors were observed, except for the Sawchuk-Zaske method, which had significantly less mean prediction error than the Hull method. The Sawchuk-Zaske method was the most reliable and accurate pharmacokinetic technique. However, because it is more costly and less convenient than the other three methods, both the accuracy and cost should be considered when selecting a method for determining serum gentamicin concentrations for a particular patient.