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Dolors Soy

Publications and source records attributed to Dolors Soy.

9 recordsLinked to original sources
PubMed2006

Are higher vancomycin doses needed in ventricle-external shunted patients?

OBJECTIVE: Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment. SETTING: Intensive Care and Neurosurgical Units. University Hospital. METHODS: Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared. MAIN OUTCOME MEASURES: Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage. RESULTS: Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005). CONCLUSIONS: Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.

Adult↗
PubMed2006

Antibacterial dosage in intensive-care-unit patients based on pharmacokinetic/pharmacodynamic principles.

PURPOSE OF REVIEW: Selection of the best antibiotic dosage regimen in intensive-care-unit patients is a critical factor for decreasing morbidity and mortality rates. The integration of pharmacokinetics and pharmacodynamics is essential to establishing an adequate therapy. Many studies on this issue have been published in recent years due to its relevance, some of which are commented upon in this review. RECENT FINDINGS: Several studies have shown that it is feasible to theoretically forecast pharmacodynamic outcomes and select the most adequate antibiotic therapy with Monte Carlo simulations. Moreover, new strategies such as the use of continuous or extended intravenous beta-lactam infusions may considerably improve therapeutic efficacy. SUMMARY: Future studies are needed in patients to assess the influence of selecting antibiotic therapy based on the impact of pharmacokinetic/pharmacodynamic on mortality, morbidity, cost, etc. It would be of special interest to evaluate this impact on patients with infections caused by multiresistant pathogens, whose mortality rates are even higher. Moreover, although studies such as this would not be easy, mainly due to the large number of patients required to obtain statistically significant results, they should be strongly encouraged because of the possible clinical and economic benefits.

Anti-Infective Agents↗
PubMed2006

Teicoplanin population pharmacokinetic analysis in hospitalized patients.

The goal of this study was to build a population pharmacokinetic (PK) model to characterize the population PK parameters in our hospitalized patients. Teicoplanin serum concentrations from clinical routine were used. Antibiotic dose history and blood collection times were recorded and analyzed with NONMEM-V. Demographic and biologic data creatinine clearance (CLcr), weight (WT), and albumin (Alb) were tested for inclusion as covariates in the basic model. Intraindividual and residual variability were modeled. One hundred seven sparse samples (mainly trough levels), from 79 patients, were included. A 2-compartment PK model characterized by clearance (CL), central compartment volume of distribution (Vc), intercompartment clearance, and steady-state volume of distribution (VSS) with first-order elimination adequately described the data. CLcr and WT significantly influenced teicoplanin CL (CL = 0.57[0.15]*(1+0.0048[0.39]*(CLcr - averageCLcr)*WT) L/h). VSS was not affected by any covariate (VSS = 50.2[0.13]L). A negative trend between Alb and individual VSS estimates was observed without statistical significance. In a new data set, bias and precision resulted in mean values of -3.24% and 9.42%, respectively. In conclusion, CLcr and WT are significant covariates on teicoplanin CL. Results from predictive accuracy and precision show the usefulness of this model for implementation in a therapeutic drug monitoring program in the near future.

Adult↗
PubMed2004

Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients.

BACKGROUND: Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity. AIM: To assess bronchial and serum concentrations of imipenem or tobramycin obtained by nebulization or instillation in critically ill mechanically ventilated patients. METHODS: Prospective randomized open trial. Eighteen patients ventilated for more than 48 h were included. Two doses of imipenem/cilastatin (1000/500 mg) separated by 8 h, or two doses of tobramycin 200 mg separated by 12 h were randomly nebulized or instilled into the tracheal tube. Five bronchoaspirates (two bronchoscopic, three blind) and five blood samples were collected on a timed schedule after the second dose. Respiratory and serum samples were analysed by HPLC, and a subset of blood samples was also evaluated by enzyme-immunoassay. RESULTS: When instilled, imipenem/cilastatin obtained higher concentrations in respiratory secretions than when nebulized (P=0.022, 1 h after the last dose; P=0.029, 2 h after the last dose). Tobramycin showed equally high concentrations when nebulized or instilled. Instillation of tobramycin may result in significant accumulation in patients with renal failure. CONCLUSIONS: High bronchial concentrations of imipenem could only be achieved by instillation, whereas tobramycin seems suitable for both modes of administration. Instillation of these antibiotics is a safe procedure that achieves high drug concentrations in respiratory secretions.

Administration, Inhalation↗
PubMed2004

Population one-compartment pharmacokinetic analysis with missing dosage data.

OBJECTIVE: Our objective was to develop a population 1-compartment pharmacokinetic (PK) method of analysis to deal with suspect or missing prior dosage history. METHODS: Population PK data from a 1-compartment model with first-order elimination and absorption, described by PK parameters clearance, volume of distribution, and absorption rate constant, are simulated. A PK sample is drawn just before a test dose (Dt), followed by a (varying) number of additional samples over 1 interdose interval (tau). For 60% of the subjects, the true history of the scheduled dose (Ds) preceding Dt differs from that prescribed, whereas doses taken before Ds do not. Two settings are evaluated: considerable accumulation of drug in the body (typical drug half-life t1/2 approximately equal to tau) and very little such accumulation (t1/2 approximately equal to tau/5). Precision and bias of several PK analysis methods--Missing Dose Method (MDM), Missing Dose Mixture Method (MDMM) and Extrapolation-Subtraction Method (ESM), all of which essentially do not use prior dose history--are compared with those of the Prescribed Dose Method (PDM), which assumes nominal dosage, and an Ideal Method (IDM), which uses true (but unknown) pre-test dose history. RESULTS: At t1/2 approximately equal to tau, MDM and MDMM are the most precise methods. The accuracy of ESM and PDM is poor. At t1/2 approximately equal to tau/5, no significant differences, in terms of precision or bias, are observed between methods. Misspecification of the structural or statistical model seems not to influence these results. The results of analysis of a real (caffeine) data set are compatible with the findings from the simulations. CONCLUSION: When a test dose is given and a predose baseline observation is taken as part of an "intensive" PK study during outpatient therapy of a 1-compartment drug, an analysis that assumes that the nominal dose history is correct is not robust to past dosage history misspecification, whereas methods that do not do this are robust and reliable.

Absorption↗
PubMed2003

Population pharmacokinetics of enfuvirtide in pediatric patients with human immunodeficiency virus: searching for exposure-response relationships.

OBJECTIVE: Our objective was to describe the population pharmacokinetics and pharmacodynamics of enfuvirtide acting on viral ribonucleic acid in children with human immunodeficiency virus 1. METHODS: A 1-compartment population pharmacokinetic model with first-order absorption and elimination was fit to subcutaneous and intravenous dose pharmacokinetic data from a 2-part study, as follows: an intensive-sample pharmacokinetic design (observed dose) (subcutaneous and intravenous, n = 12) followed by a sparse-sample design (unobserved dose) (subcutaneous, n = 15). The parameters of this model are clearance (CL), volume of distribution (V), absorption rate (k(a)), bioavailability (F), and both interindividual and residual variability. Plasma ribonucleic acid concentrations over time were used to build a population viral pharmacodynamics model with the following parameters: viral clearance (CL(v)), initial viral concentration (A(0)), duration (tau) and rate (R) of preinfected cell-based viral input after enfuvirtide was begun, and interindividual and residual variability. RESULTS: The mean population CL and V of enfuvirtide for a child with a mean body weight of 21.3 kg were 1.42 L/h and 5.67 L, respectively. Patient weight affected CL and V. Volume appeared to differ between intensive and sparse sampling occasions, and this difference also affected the residual error variance. Time after the beginning of therapy did not significantly affect any pharmacokinetic parameter, supporting the absence of metabolic induction and inhibition. Although trends were present, no statistically significant relationship was seen between any pharmacokinetic-based individual enfuvirtide exposure measure and any virologic response measure. CONCLUSIONS: Regarding pharmacokinetics and pharmacodynamics, no statistically significant correlation between exposure measures and viral clearance was observed.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

[Reflections on betalactam antibiotics administered by continuous infusion].

Numerous studies on continuous intravenous infusion of betalactam antibiotics have indicated that this could be a useful strategy for treating nosocomial infections as well as exacerbations of pulmonary infections in patients with cystic fibrosis and episodes of febrile neutropenia. From the pharmacodynamic viewpoint, betalactam antibiotics have a time-dependent behavior. Thus, the pharmacokinetic/pharmacodynamic index that best correlates with therapeutic efficacy appears to be the time during which free antibiotic concentrations remain above the minimum inhibitory concentration (MIC) of the infecting microorganism. Continuous infusion of betalactams successfully optimizes this pharmacokinetic/ pharmacodynamic index. Furthermore, some studies have shown that this therapeutic strategy may be favorable economically.

Anti-Bacterial Agents↗