Therapeutic drug monitoring
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The controversy still surrounds the optimal dosing regimen of tranexamic acid (TA), primary antifibrinolytic agent used in high-risk surgeries. This study compares the pharmacokinetics profile obtained from the group of patients undergoing heart surgery with the use of cardiopulmonary bypass (CPB) with the theoretical model currently used as an established dosing regimen of TA in cardiac surgery. ⋯ The suitability of automated solid-phase microextraction for high-throughput clinical analysis was established for the first time. The obtained pharmacokinetic profiles showed significant interpatient variation in the concentration of TA during heart surgery with the use of CPB, which confirms the need of the therapeutic monitoring of this antifibrinolytic agent.
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Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. ⋯ In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response.
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Clinical Trial
Pharmacokinetic evaluation of voriconazole treatment in critically ill patients undergoing continuous venovenous hemofiltration.
Voriconazole represents an essential part of antimicrobial therapy in critically ill patients. The aim of this study was to exclude a significant alteration in voriconazole pharmacokinetics in critically ill patients undergoing continuous venovenous hemofiltration (CVVH). ⋯ The clearance of voriconazole by CVVH is not clinically significant. In view of this finding, voriconazole dose adjustment in patients undergoing the standard method of CVVH is not required. However, the observed potential for an unpredictable voriconazole accumulation suggests the usefulness for monitoring its levels in critically ill patients.
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Although risperidone is commonly used in the acute and maintenance treatment of schizophrenia, the role of therapeutic drug monitoring has yet to be elucidated. The purpose of this review was to determine whether risperidone warrants therapeutic drug monitoring in patients with schizophrenia. ⋯ The routine use of risperidone levels does not seem warranted in all patients with schizophrenia. Clinical end points (ie, response and toxicity) should be monitored by assessing changes in symptoms and emergence of adverse effects, especially extrapyramidal symptoms. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential noncompliance and supporting compliance, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions, adverse effects, and use in special populations.
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Because the sepsis-induced pharmacokinetic (PK) modifications need to be considered in aminoglycoside dosing, the present study aimed to develop a population PK model for amikacin (AMK) in severe sepsis and to subsequently propose an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters. Concentration-time profiles for AMK were obtained from 88 critically ill septic patients during the first 24 hours of antibiotic treatment. The population PK model was developed using a nonlinear mixed effects modeling approach. ⋯ Predictive performance of individual Bayes estimates computed using the proposed optimal sampling strategy was reported: mean prediction errors were less than 5% and root mean square errors were less than 30%. The present study confirmed the significant influence of the creatinine clearance on the PK disposition of AMK during the first hours of treatment in critically ill septic patients. Based on the population estimates, an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters was developed, meeting the need of clinical practice.