Markov-Chain Monte Carlo Bayesian Analysis (BAYES, NUTS)Ģ.Stochastic Approximation Expectation-Maximization (SAEM).Importance Sampling Expectation-Maximization (IMP).First Order Conditional Estimation (FOCE).Population analysis methods available for handling a variety of PK/PD population analysis problems: MATLAB simulations of dosing schedules for use in future studies predicted that 12 g given over 6, 8, or 12 h will provide concentrations above the K(m) of endothelial cell CAT-1 transporters in 90%, 75%, and 60% of patients, respectively.The latest release of NONMEM ® includes these enhancements and more.ġ. Weight and ethnicity were significant covariates for clearance.
The half-life of exogenous L-arginine was reduced in patients with malaria compared with that for healthy adults. The natural time course of L-arginine recovery was described empirically by a second-order polynomial with a time to half recovery of 26 h. A two-compartment linear model with first-order elimination best described the data, with a clearance of 44 liters/h (coefficient of variation = 52%) and a volume of distribution of 24 liters (CV = 19%). The data were analyzed using a population approach with NONMEM software. Patients who had not received L-arginine were also assessed and included in the model. In doses of 3, 6, or 12 g,L-arginine was infused over 30 min to 30 adults with moderately severe malaria, and plasma concentrations were measured at 8 to 11 time points. We developed a pharmacokinetic model for L-arginine in moderately severe malaria to explore the concentration-time profile and identify important covariates. Supplementation with L-arginine has the potential to improve NO bioavailability and outcomes.
Severe malaria is associated with decreased nitric oxide (NO) production and low plasma concentrations of L-arginine, the substrate for NO synthase.
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