In this study, which involved on average only two serum concentrations of caffeine per patient, the use of NONMEM gave us significant and consistent information about the pharmacokinetic profile of caffeine when compared with available bibliographic information. Additionally, parenteral nutrition and low gestational age (< or = 28 weeks) may even come to be considered as risk factors, and their presence may serve as an indicator of the need for periodic monitoring of caffeine concentrations in premature infants.

The aim of this study was to adapt the vancomycin therapeutic range to the kinetic models usually employed in clinical settings (one- and two-compartment models). Estimates of vancomycin pharmacokinetic parameters were obtained for both models in 22 hematologically malignant patients on vancomycin treatment using two serum concentrations and a bayesian algorithm. From these individually estimated pharmacokinetic parameters, an estimation of the maximum (Cssmax), 2 h postinfusion (Css2), and minimum (Cssmin) steady-state vancomycin serum concentrations for the one- and two-compartment models was made for a fixed 30 mg/kg/day dose. The linear regression equations between the predicted Css2 and Cssmin for the one- and two-compartment models do not differ significantly from the identity line, whereas the corresponding equation for Cssmax points to a 61% underestimation of Cssmax when the one-compartment model is used. From this latter regression equation, it is possible to define 20 mg/L (range of 18-21 mg/L) as a target Cssmax vancomycin serum concentration when a one-compartment model is used to monitor vancomycin therapy. Another practical approach would be to define the target concentration by a desired range at 2 h, which corresponds to a Cssmax value of 30-40 mg/L.

The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses.

No abstract

Analytical interferences in digoxin immunoassays constitute a well-known problem, with repercussions for therapeutic drug monitoring. Clinically effective doses of spironolactone and potassium canrenoate cross-react in several digoxin immunoassays, producing falsely elevated or lowered concentrations. This study evaluates the interferences caused by these drugs in the microparticle enzyme immunoassay (MEIA III) in comparison with another 3 immunoassays used for digoxin therapeutic drug monitoring: MEIA II, fluorescence polarization immunoassay, and enzyme multiplied immunoassay. The potential clinical implications of assay discrepancies in patient care are also assessed. To evaluate assay performance, in vitro specimens and real patient samples were measured using the 4 assays. Five serum pools were spiked with digoxin to achieve concentrations of 1 and 2.25 ng/mL digoxin and measured with the immunoassays before and after supplementation. Real samples from patients receiving digoxin (n = 39), digoxin and spironolactone (n = 35), or digoxin and potassium canrenoate (n = 4) were also quantified. The influence of ultrafiltration was evaluated in 3 pools from 29 additional patients. The implications of assay discrepancies for dose recommendations were also evaluated. In general, the results obtained for the in vitro and in vivo approaches coincided, confirming statistically significant differences in the assays regardless of the type of sample. MEIA III showed positive interference against the well-known negative interference attributed to MEIA II. According to Bland-Altman analysis, it is not possible to assume the interchangeability of the immunoassays evaluated. Thus, individual patients must be monitored with the same technique even in the absence of potential interferences. Discordant digoxin dose recommendations were estimated in 31% of patients not treated with interfering drugs and in 43% of cotreated patients. From a clinical perspective, analytical interferences in digoxin immunoassays are a real and frequent problem, which seems even more important in view of the lower therapeutic range now recommended.