Therapeutic drug monitoring
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Whole-blood concentrations of the immunosuppressant drugs everolimus and sirolimus should be monitored. A sensitive and selective method offering the detection of both analytes in small sample volumes would optimize the throughput of samples for sirolimus or everolimus analysis. This study reports the validation of a liquid chromatography tandem mass spectrometry method, including a stable isotope internal standard, for the simultaneous measurement of everolimus and sirolimus. ⋯ A straightforward, robust liquid chromatography tandem mass spectrometry assay has been developed and validated for the simultaneous measurement of everolimus and sirolimus in small volumes of whole blood.
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Valproic acid (VPA) is widely used to treat various types of epilepsy. Interindividual variability in VPA pharmacokinetics may arise from genetic polymorphisms of VPA-metabolizing enzymes. This study aimed to examine the relationships between plasma VPA concentrations and the -161C>T single nucleotide polymorphism in uridine diphosphate glucuronosyltransferase (UGT) 2B7 genes in pediatric epilepsy patients. ⋯ These data suggest that the UGT2B7 -161C>T polymorphism in pediatric epilepsy patients carrying the CYP2C9*1/*1 genotype affects VPA concentration.
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Randomized Controlled Trial
A randomized double-blind clinical trial of a continuous 96-hour levobupivacaine infiltration after open or laparoscopic colorectal surgery for postoperative pain management--including clinically important changes in protein binding.
Continuous local anesthetic infiltration has been used for pain management after open colorectal surgery. However, its application to patients undergoing laparoscopic colorectal surgery has not been examined. The aim of this prospective, randomized, double-blind, placebo-controlled clinical trial was to study the use of a commercial infiltration device in patients undergoing open or laparoscopic colorectal surgery, along with plasma concentrations of levobupivacaine, its acute-phase binding protein (alpha-1 acid glycoprotein, AAG), and the stress marker, cortisol. ⋯ Continuous local anesthetic infiltration may be more beneficial in open surgery. The threshold for adverse effects from highly bound local anesthetic drugs established in healthy volunteers is of limited usefulness in clinical scenarios in which AAG concentration increases in response to surgical stress. Hence, there is scope to adopt higher doses to enhance therapeutic benefit.
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Controlled Clinical Trial
Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.
Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. ⋯ The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.
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While perceived safe in pregnancy, several recent studies raise concerns about both fetal and maternal safety of ondansetron. Until more data are available, it should not be a first-line medication for morning sickness.