Comparison of gas-liquid chromatography and fluorescence polarization immunoassay for therapeutic drug monitoring of flecainide acetate.

A gas chromatographic (GC) method for quantitation of flecainide acetate in human plasma is described and compared with a fluorescence polarization immunoassay (FPIA) for therapeutic drug monitoring. The GC method includes a solid-phase extraction procedure and electron capture detection (ECD) without the need of derivatization. Within-day and between-day coefficients of variation were less than 7% of GC and FPIA. Recovery was between 89-101% for the GC method. Plasma from 36 patients were analysed by both GC and FPIA and the results showed a good correlation (slope = 0.96; intercept = 0.009 micrograms ml-1; r = 0.987).

Simple kinetic model for the study of lactate metabolic adaptation to exercise in sportsmen routine evaluation.

The interindividual specific lactate metabolic adaptation to exercise has been studied. A simple kinetic model was used which did not require labelled molecules. An one open compartment model with a first-order release rate constant described the release of lactate from the muscle. Six volunteers performed five times the same session: pedaling as long as possible at 400 W and 110 rpm. The lactate concentration was measured along the 60 min of recovery. The theoretical curve corresponding to the model was fitted to the experimental data using a non-linear regression method. The values of the following kinetic parameters were obtained: elimination rate constant (ke), release rate constant (ka), apparent amount released into the compartment divided by the volume of distribution (FQo/Vd) and area under the lactate concentration-time curve (AUC). Two way-ANOVA, Scheffé test and discriminant analysis were used to test the statistical significance of these parameters. No significant intra-individual variations were shown. Significant differences were observed between subjects (ke: P = 0.0020; ka: P less than 0.0001; FQo/Vd: P = 0.0002; AUC: P = 0.0395). A correlation was also found between FQo/Vd and ke (r = 0.72; P less than 0.001). In conclusion, the computed parameters provided by the model are sufficient to discriminate and characterize the metabolic response of each subject after short and intensive exercises.

Variations in lactate apparent clearance during rest and exercise in normal man.

The purpose of this study is to present a simple kinetic model for the study of the lactate metabolism. This model based on pharmacokinetic theory, does not require labelled molecules and yields a finer approach to lactate metabolism than does a simple observation of blood lactate concentration. The variations in parameter values have been studied in six male subjects after intensive exercise (385 W, 110 rpm and 1 min) (IE) followed by three different recovery periods: passive recovery (RE), moderate exercise (ME) and heavy exercise (HE). Blood lactate concentration was measured prior to IE and during the first hour of recovery. After mathematical treatment, the results show that the apparent clearance increases 2.83 +/- 0.76 fold from RE to ME and 1.96 +/- 0.61 fold from RE to HE. The steady state blood lactate concentration induced by the intensity of recovery (La(ss)) increases slightly (1.53 +/- 0.37 fold) from RE (1.40 +/- 0.36 mmol.l-1) to ME (2.04 +/- 0.32 mmol.l-1). Then La(ss) increases markedly (3.78 +/- 0.91 mmol.l-1) during HE (2.81 +/- 0.78 fold the La(ss) value at RE). The ratio between the apparent rates of lactate production (F"K0) during RE, ME and HE was calculated. F"K0 increases in a linear way versus intensity of exercise recovery. It was concluded that in the human: 1) the blood lactate concentration is not an accurate indicator of lactate production, 2) in our experiment, the apparent lactate production is a linear function of exercise intensity and 3) the abruptly increasing blood lactate concentration at a high level of exercise intensity is due to a decrease in apparent clearance.

The maximum lactate clearance: a new concept to approach the endurance level of an athlete.

The purpose of this study is to present a mathematical model based on physiological observations which describes the evolution of the blood lactate concentration ([LA-]) versus the oxygen uptake (VO2) during a continuous graded exercise test. This model is based on several assumptions: 1) [LA-] reflects the balance between the rates of appearance and disappearance of the lactate in the blood compartment; 2) VO2 measured at the end of each step, is a linear function of the power output and thus of the time; 3) the appearance rate of lactate into the blood is an exponential function of VO2; 4) the rate of disappearance is a saturable process which can be modelized by Michaelis-Menten kinetics; 5) the volume of distribution of lactate in the blood compartment is a constant during exercise. The parameters used in this model correspond to the integration of several biochemical and physiological phenomenons. The originality of this approach is to express the rate of lactate appearance and disappearance versus VO2 rather than time. Whatever the general pattern of the data, the fitted curve gives always very good results. Especially, the theoretical curve fits the decrease in [LA-] usually observed during the first steps of such an exercise. From the computed parameters the evolution of lactate clearance during a continuous graded exercise test may be modelized. A strong relationship exists between the level of endurance training and the maximum lactate clearance (Clmax) reached during the exercise test. The VO2 for Clmax is an indicator of the shift of the relationship [LA-]-VO2. Then, we propose to use the maximum lactate clearance which is individually determined, to characterize the endurance level of an athlete.