Linear relationships in systems with non linear kinetics.
The elimination rate of drug from a capacity-limited one-compartment model can be expressed by equation (1): [formula: see text] Traditionally equation (1) was linearized according to equation (2): [formula: see text] Here, an alternative linear relationships between concentration and the area under the curve of C/(Km + c]) is proposed: [formula: see text] By iteration of Km into equation (3) until the statistic of analysis of variance for the regression is maximized, both Km and Vmax can be obtained. Several cases were considered: a) Intravenous bolus (single dose): Km (mg/L), Vmax (mg/L h), Vd (L) and V (mg/h) can be estimated. b) Extravascular administration (single dose): by the method of residuals it is possible to make additional estimations of FD/Vd (mg/L) and Ka (1/h). c) Bioequivalence studies: with parameters obtained at single dose, the simulated levels at steady-state are considered for the bioequivalence assessments. d) Km, Vmax estimation with two (C,t) points (single dose): double iteration (Km values and interpolated fictitious third points) are needed. e) Multiple dose: [formula: see text] If t2-t1 = T (interval of administration) it is possible to calculate operatives Km, Vmax, FD/Vd and to estimate Css (steady-state concentration). C1 and C2 correspond to different intervals. All the areas were calculated by the trapezoidal rule.
Fagiolino
P
P
Laboratorio de Farmacodinamia, Facultad de Química, Montevideo, Uruguay.
Savio
E
E
Stareczek
S
S
D001682:Biological Availability; D001711:Biotransformation; D006801:Humans; D007275:Injections, Intravenous; D008954:Models, Biological; D010599:Pharmacokinetics; D010672:Phenytoin / Q000493:pharmacokinetics; D012044:Regression Analysis; D012984:Software; D013806:Theophylline / Q000493:pharmacokinetics
D010672:Phenytoin; D013806:Theophylline