Limited sampling strategy for estimation of amikacin optimal sampling time in critically ill adults.

Aminoglycosides are a class of antibiotics that are commonly used in the treatment of gram-negative pathogens in the critically ill population. Unfortunately, dosing of these aminoglycosides in critically ill patients is difficult due to their altered pharmacokinetics in the critically ill and narrow therapeutic index. In this study, we evaluated whether a limited sampling strategy can be used to predict the area under the concentration (AUC) curve of amikacin concentrations over a 24-hour period after a single dose of intravenous amikacin (25 mg/kg). This open-labelled, non-comparative prospective study recruited 20 adult critically ill trauma patients with a diagnosis of hospital-acquired infection. We assessed the best estimate of plasma amikacin concentrations over a 24-hour period by multiple stepwise regression, using nine blood samples during this study period as the gold standard. Using a jackknife procedure, the AUC of amikacin over a 24-hour period was estimated by choosing a combination of the amikacin concentrations measured at different time-points. Overall, the mean prediction error of all models was not statistically different from zero (P >0.05). Based on bias and imprecision, all models gave good estimate of AUC of amikacin over a 24-hour period, but a two-point sampling strategy at 1.5 and 6 hours post-dose appeared to offer the best compromise between accuracy and cost-effectiveness in optimising the dosing of amikacin in critically ill patients.

Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients.

BACKGROUND AND OBJECTIVES: Severe sepsis is a major problem as cause of high rates morbidity and mortality in intensive care units (ICU). Aminoglycosides are an important group of antimicrobials used for severe sepsis. However, aminoglycoside pharmacokinetics in ICU patients may be altered during sepsis, which can affect the drug concentrations. Therefore, this study was undertaken to examine the relationship between amikacin disposition kinetics after a 25 mg/kg loading dose and hemodynamic response to sepsis, as well as clinical parameters, in a population of critically ill patients. METHODS: In this work, 30 patients who were candidate to amikacin therapy following Gram negative sepsis were enrolled. The pharmacokinetic profile of amikacin by a non-compartmental model was calculated for each patient. RESULTS: Mean volume of distribution was 0.36 ± 0.07 L/kg and mean serum amikacin clearance was 3.88 ± 0.97 ml/min/kg. In the case of Vd, APACHE II score correlation was significant. In the case of amikacin clearance, two covariates including creatinine clearance and Sr Cr significant correlation was found. CONCLUSIONS: It appears necessary to use higher amikacin dosage (≥ 25 mg/kg) considering hemodynamic response of patients to sepsis. To achieve therapeutic drug concentration a close drug monitoring and a shift from the population mean toward a value more representative of the critically ill patient subpopulation is crucial.  

Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization.

To investigate the effects of silymarin on follicular development, we enrolled 40 healthy women undergoingin vitro fertilization (IVF) due to male factor infertility in this trial. They underwent ovulation induction and on a random and blind basis, patients were assigned to receive silymarin (70 mg x 3/day) or placebo from the beginning of the induction cycle. The number and quality of oocytes retrieved were evaluated and apoptosis of > or = granolusa cells was studied. There was no significant difference between the groups for mean number of follicles 18 mm (P = 0.131), mean number of oocytes retrieved (P = 0.209) or endometrial thickness (P = 0.673). However, the proportion of total apoptosis in the study group was significantly lower than in the placebo group (P = 0.032). These data suggest that administration of silymarin in IVF patients concomitantly with gonadotropin results in reduction of granolusa cell apoptosis but does not have any effect in promotion of follicular development, oocyte retrieval or endometrial thickness.

Evaluation of effect of silymarin on granulosa cell apoptosis and follicular development in patients undergoing in vitro fertilization

To investigate the effects of silymarin on follicular development, we enrolled 40 healthy women undergoing in vitro fertilization [IVF] due to male factor infertility in this trial. They underwent ovulation induction and on a random and blind basis, patients were assigned to receive silymarin [70 mg X 3/day] or placebo from the beginning of the induction cycle. The number and quality of oocytes retrieved were evaluated and apoptosis of granolusa cells was studied. There was no significant difference between the groups for mean number of follicles >/= 18 mm [P = 0.131], mean number of oocytes retrieved [P = 0.209] or endometrial thickness [P = 0.673]. However, the proportion of total apoptosis in the study group was significantly lower than in the placebo group [P = 0.032]. These data suggest that administration of silymarin in IVF patients concomitantly with gonadotropin results in reduction of granolusa cell apoptosis but does not have any effect in promotion of follicular development, oocyte retrieval or endometrial thickness

Estimation of abbreviated mycophenolic acid area under the concentration-time curve during early posttransplant period by limited sampling strategy.

Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to optimize therapeutic drug monitoring during the early post-renal transplant period. The aim of this study was to develop a limited sampling strategy to estimate an abbreviated MPA AUC within the first month after renal transplantation. In this study we selected 19 patients in the early posttransplant period with normal renal graft function (glomerular filtration rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to derive model equations best fitted to MPA AUC(0-12h). The regression equation for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547 (r(2) = .882). The validation of the method was performed using the jackknife method. Mean prediction error of this model was not different from zero (P > .05) and had a high root mean square prediction error (8.06). In conclusion, this limited sampling strategy provided an effective approach for therapeutic drug monitoring during the early posttransplant period.