Additive and proportional error nonmem with random effect

The dose of enoxaparin should be individualized to the patients' renal function and weight. These best doses were selected based on providing the lowest equal probability of either being above or below the therapeutic range and the highest probability that the C(ss) achieved would lie within the therapeutic range. The best doses for patients in the general medical unit were 60 IU kg(-1) per 12 h (5.0 IU kg(-1) h(-1)) if CrCL 50 ml min(-1). Simulations suggested that the best doses for patients in the ICU setting were 50 IU kg(-1) per 12 h (4.2 IU kg(-1) h(-1)) if CrCL 50 ml min(-1). Both CrCL and weight were found to affect significantly clearance and volume of distribution of the central compartment, respectively. The best dose was selected based on the highest probability that the C(ss) achieved would lie within the therapeutic range.ДЄ two-compartment linear model with additive and proportional residual error for general medical unit patients and only a proportional error for patients in ICU provided the best description of the data. Values can be 0, 1, or 2 with the folowing meaning 0: no random effect is used (fixed to 0, independently of value defined in IIVvalues0 1: the random effect parameter is estimated (default if IIVestimate not defined) 2: the random effect parameter is kept fixed on its initial guess Here: There is no random effect on the GAM coefficient.

Monte Carlo simulations were used to (i) evaluate covariate effects on C(ss) and (ii) compare the impact of different infusion rates on predicted C(ss).

The effects of age, body size, height, sex, creatinine clearance (CrCL) and patient location on pharmacokinetic (PK) parameters were evaluated. These were combined with 309 anti-Xa concentrations from 35 patients who received subcutaneous enoxaparin. Three hundred and sixty-three anti-Xa concentration measurements were available from patients who received CII. To develop an appropriate dosing strategy for continuous intravenous infusions (CII) of enoxaparin by minimizing the percentage of steady-state anti-Xa concentration (C(ss)) outside the therapeutic range of 0.5-1.2 IU ml(-1).ДЄ nonlinear mixed effects model was developed with NONMEM for 48 adult patients who received CII of enoxaparin with infusion durations that ranged from 8 to 894 h at rates between 1 IU h(-1).

Additive and proportional error nonmem with random effect