Blood Levels Of Drug Research Articles

Use of NOACS in Extremes of Body Weight

Certain physiological phenomena in our body lead to severe changes in body weight leading to obesity. If needed, currently, there is no specific regimen for using novel oral anticoagulants (NOACs) in obese patients. It has been found that fixed doses of NOACs bring out more drug exposure to lower BMI patients, whereas it brings out lesser blood drug levels in patients with higher BMI.1 When researchers evaluated NOACs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE), most randomized trials did not exclude body weight from the studies. Hence, the subgroup analysis of these trials showed no considerable difference in outcomes in obese patients.2 The International Society on Thrombosis and Haemostasis showed that NOACs are safer in patients with a body weight of ≤ 120 kg (BMI ≤40 kg/m2) at the usual dose as compared to patients with a body weight of >120 kg (BMI >40 kg/m2).2 Several retrospective studies have shown suboptimal plasma concentrations (in 20%-28% of obese patients studied) with dabigatran and rivaroxaban compared to apixaban.3 Dose reduction is recommended for apixaban if body weight is ≤ 60 kg (in addition to age and renal function). Reduction in the dose of edoxaban is recommended due to the pharmacokinetic property of high systemic exposure in low body weight patients.4 For patients with body weight > 120 kg or BMI > 40 kg/m2, it is suggested to use rivaroxaban and apixaban, while dabigatran, edoxaban, and betrixaban should be avoided.5 For patients with a body weight <60 kg, renal function should be assessed before adjusting the dose of NOACs. These patients overestimate renal function due to lower body muscle mass. Old age and frailty should also be considered, as these factors are related to bad outcomes in patients with low body weight.6 It is suggested to use apixaban (after taking a renal impairment and age into consideration) and edoxaban with caution in low-body weight patients.7 Dabigatran serves as a less-than-ideal drug for low-body weight patients due to high systemic exposure. No conclusive data is available for rivaroxaban.8 Due to a lack of clinical interest in this population subset of extreme body weight changes, we need more data, which leads to the need for more extensive work in this domain, revealing clear answers in the future.

Changes in Psychotropic Drug Blood Levels After SARS-CoV-2 Vaccination: A Two-Center Cohort Study.

Limited evidence from case reports suggests that coronavirus disease 2019 (COVID-19) vaccination may interact with the treatment outcomes of psychiatric medications. Apart from clozapine, reports on the effect of COVID-19 vaccination on other psychotropic agents are scarce. This study aimed to investigate the impact of COVID-19 vaccination on the plasma levels of different psychotropic drugs using therapeutic drug monitoring. Plasma levels of psychotropic agents, including agomelatine, amisulpride, amitriptyline, escitalopram, fluoxetine, lamotrigine, mirtazapine, olanzapine, quetiapine, sertraline, trazodone, and venlafaxine, from inpatients with a broad spectrum of psychiatric diseases receiving COVID-19 vaccinations were collected at 2 medical centers between 08/2021 and 02/2022 under steady-state conditions before and after vaccination. Postvaccination changes were estimated as a percentage of baseline. Data from 16 patients who received COVID-19 vaccination were included. The largest changes in plasma levels were reported for quetiapine (+101.2%) and trazodone (-38.5%) in 1 and 3 patients, respectively, 1 day postvaccination compared with baseline levels. One week postvaccination, the plasma levels of fluoxetine (active moiety) and escitalopram increased by 31% and 24.9%, respectively. This study provides the first evidence of major changes in the plasma levels of escitalopram, fluoxetine, trazodone, and quetiapine after COVID-19 vaccination. When planning COVID-19 vaccination for patients treated with these medications, clinicians should monitor rapid changes in bioavailability and consider short-term dose adjustments to ensure safety.

Lactated Ringer as Preservation Solution in Living Donor Renal Transplantation

Optimal organ preservation remains a critical hallmark event in renal transplantation as it is the supply line. Previous studies have shown that the choice of preservation solution may affect transplant outcomes. In this study, we aimed to present the early follow-up results of the graft and patients, using lactated Ringer to preserve kidney allografts with living donors. The results of 97 living donor transplant operations performed in Sanko University Hospital were evaluated retrospectively. The patient's evaluation included demographics, dialysis time duration, renal replacement method, primary disease, comorbidity, surgical and clinical complications in the acute period, graft functions, blood levels of calcineurin inhibitor drugs, anastomotic renal artery, warm ischemia, and cold ischemia times. Donor (49 men, 50.5%) and recipient (58 men, 59.7%) demographics, HLA compatibility (mismatch), hospitalization days, and length of warm and cold ischemic time are summarized in Table 1. Primary nonfunction was not defined in any patients, but delayed graft function was observed during the follow-up of 3 patients (3.09%), who were all hypotensive in the post-transplantation period, and positive inotropic infusion was needed for hemodynamic stability. Lactated Ringer demonstrated efficacy in terms of patient and graft survival, and its lower cost represents a financial advantage, so it can be used in living donor kidney transplantation because it is safe, effective, and inexpensive. Standard preservation solutions may still be recommended in cases with long cold ischemia times, such as paired exchange transplants and cadaveric transplants. Thus, randomized controlled studies are needed for further investigation.

Central Versus Peripheral Drug Exposure Ratio, a Key Differentiator for Siponimod Over Fingolimod?

Siponimod, a potent and selective sphingosine-1-phosphate (S1P1,5) agonist, is the only therapeutic agent that has shown efficacy against disability progression, decline in cognitive processing speed, total brain volume loss, gray matter atrophy and signs of demyelination in patients with secondary progressive multiple sclerosis (SPMS). Although the pathophysiology of progression in SPMS and primary progressive MS (PPMS) is thought to be similar, fingolimod, the prototype S1P1,3,45 agonist, failed to show efficacy against disability progression in PPMS. Differentiating siponimod from fingolimod at the level of their central effects is believed to be the key to a better understanding of the underlying characteristics that could make siponimod uniquely efficacious in progressive MS (PMS). Here, we compared the central vs. peripheral dose-dependent drug exposures for siponimod and fingolimod in healthy mice and mice with experimental autoimmune encephalomyelitis (EAE). Siponimod treatment achieved dose-dependent efficacy and dose-proportional increases in steady-state drug blood levels, with a central nervous system (CNS)/blood drug-exposure ratio (CNS/bloodDER) of ~ 6 in both healthy and EAE mice. In contrast, fingolimod treatments achieved dose-proportional increases in fingolimod and fingolimod-phosphate blood levels, with respective CNS/bloodDER that were markedly increased (≥ threefold) in EAE vs. healthy mice. If proven to have translational value, these observations would suggest that CNS/bloodDER may be a key differentiator for siponimod over fingolimod for clinical efficacy in PMS.

Evaluation of the meropenem dosage and administration schedule in patients with bacteremia initial therapy

BackgroundThe standard meropenem (MEPM) regimen allowed by insurance in Japan is 0.5 g two or three times a day. Differences in dosages and administration schedules in Japan were evaluated. MethodsPatients with bacteremia for whom MEPM was used as the initial treatment at our institution between 2016 and 2021 were included. We retrospectively investigated patients classified into two groups: those treated according to severe infections (high-dose groupand others (low-dose group). After propensity score matching, we compared the probability of achieving free drug blood levels above the minimum inhibitory concentration (MIC) in 24 h (%fT > MIC) and outcomes. ResultsThe probability of 100% fT > MIC was significantly higher in the high-dose group (96.4% vs 74.5%, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2–0.4, P = < 0.001). Regarding outcomes, the 30-day mortality rate was significantly lower in the high-dose group (1.4% vs. 11.4%, OR = 8.0, 95% CI = 1.5–43.7, P = 0.019). ConclusionsTo improve outcomes in patients with bacteremia treated with MEPM, support for appropriate antimicrobial use is necessary for compliance with the dosage and administration schedule according to severe infections in initial treatment.

Kinase-Modulated Bioluminescent Indicators Enable Noninvasive Imaging of Drug Activity in the Brain.

Aberrant kinase activity contributes to the pathogenesis of brain cancers, neurodegeneration, and neuropsychiatric diseases, but identifying kinase inhibitors that function in the brain is challenging. Drug levels in blood do not predict efficacy in the brain because the blood-brain barrier prevents entry of most compounds. Rather, assessing kinase inhibition in the brain requires tissue dissection and biochemical analysis, a time-consuming and resource-intensive process. Here, we report kinase-modulated bioluminescent indicators (KiMBIs) for noninvasive longitudinal imaging of drug activity in the brain based on a recently optimized luciferase-luciferin system. We develop an ERK KiMBI to report inhibitors of the Ras-Raf-MEK-ERK pathway, for which no bioluminescent indicators previously existed. ERK KiMBI discriminates between brain-penetrant and nonpenetrant MEK inhibitors, reveals blood-tumor barrier leakiness in xenograft models, and reports MEK inhibitor pharmacodynamics in native brain tissues and intracranial xenografts. Finally, we use ERK KiMBI to screen ERK inhibitors for brain efficacy, identifying temuterkib as a promising brain-active ERK inhibitor, a result not predicted from chemical characteristics alone. Thus, KiMBIs enable the rapid identification and pharmacodynamic characterization of kinase inhibitors suitable for treating brain diseases.

Rejection markers in kidney transplantation: do new technologies help children?

Recent insights in allorecognition and graft rejection mechanisms revealed a more complex picture than originally considered, involving multiple pathways of both adaptive and innate immune response, supplied by efficient inflammatory synergies. Current pillars of transplant monitoring are serum creatinine, proteinuria, and drug blood levels, which are considered as traditional markers, due to consolidated experience, low cost, and widespread availability. The most diffuse immunological biomarkers are donor-specific antibodies, which are included in routine post-transplant monitoring in many centers, although with some reproducibility issues and interpretation difficulties. Confirmed abnormalities in these traditional biomarkers raise the suspicion for rejection and guide the indication for graft biopsy, which is still considered the gold standard for rejection monitoring. Rapidly evolving new "omic" technologies have led to the identification of several novel biomarkers, which may change the landscape of transplant monitoring should their potential be confirmed. Among them, urinary chemokines and measurement of cell-free DNA of donor origin are perhaps the most promising. However, at the moment, these approaches remain highly expensive and cost-prohibitive in most settings, with limited clinical applicability; approachable costs upon technology investments would speed their integration. In addition, transcriptomics, metabolomics, proteomics, and the study of blood and urinary extracellular vesicles have the potential for early identification of subclinical rejection with high sensitivity and specificity, good reproducibility, and for gaining predictive value in an affordable cost setting. In the near future, information derived from these new biomarkers is expected to integrate traditional tools in routine use, allowing identification of rejection prior to clinical manifestations and timely therapeutic intervention. This review will discuss traditional, novel, and invasive and non-invasive biomarkers, underlining their strengths, limitations, and present or future applications in children.

S-52-5: MEASURING DRUG LEVELS USING A DRIED BLOOD SPOT COMBINED WITH PERSONALIZED FEEDBACK TO IMPROVE RESISTANT HYPERTENSION: A RANDOMIZED CONTROLLED TRIAL

Introduction: Identification of non-adherence to antihypertensive drugs is crucial to improve resistant hypertension (RH). For this therapeutic drug monitoring is the most reliable method. Objectives: The primary objective of this study is to determine whether drug levels measured with a dried blood spot (DBS) method combined with personalized feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Design and method: This is a multi-center single-blinded randomized controlled trial (RHYME-RCT, NL6736). Eligible patients based on previous blood pressure readings underwent DBS sampling and a 24-hour ambulatory blood pressure measurement (ABPM) simultaneously. Patients with a daytime systolic blood pressure (SBP) &gt; 135 and/or diastolic blood pressure (DBP) &gt; 85 mmHg were randomized to a standard treatment (control) arm or intervention arm. The intervention was performed by the treating physician and included information on drug levels and a personalized feedback conversation based on a feedback tool. The follow-up period was one year and included visits at 3, 6 and 12 (T = 12) months inclusion. At each visit an 24h-ABPM and DBS were performed. Results: A total of 141 patients were measured at baseline, of which 100 patients had blood pressures &gt; 135/85 mmHg and were randomized to the intervention (n = 49) or control arm (n = 51). The adherence rate in the excluded population (n = 41) was 78.0%. The randomized patients had a mean age of 59.4 ± 11 years and were predominantly male (70.0%). The prevalence of RH decreased from 100% in both arms to 73.2% at T = 12 in the intervention arm (p = 0.002, n = 37) and 59.1% at T = 12 in the control arm (p &lt; 0.001, n = 41). Adherence rates improved from 67.3% to 92.1% in the intervention arm (p = 0.021) and 68.6% to 71.4% in the control arm (p = 1.000). This increase in adherence was significantly higher in the intervention arm compared to the control arm (p = 0.018). No statistically significant difference was found after 12 months between the two arms in the degree of RH (p = 0.171), SBP (p = 0.297) or DBP (p = 0.655). Conclusions: Measuring blood pressure and drug levels led to a decrease in the prevalence of RH in both arms and improved non-adherence in the intervention arm. However, the improvements in adherence did not lead to a lower blood pressure and degree of having RH. The fact that one third was excluded at baseline because of normotension suggests that participation in a study already leads to improvement of adherence and thus blood pressure control.

Is psilocybin an effective antidepressant and what is its Mechanism of action?

Goodwin etal.1 report a single 25mg dose of psilocybin has an antidepressant effect short-term in medication-resistant depression. Unanswered questions include drug blood level as a guide to dose, psychedelic effects relationship to antidepressant benefit, and potential suicide risk of psilocybin.

Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.

Therapeutic drug monitoring (TDM) receives growing interest in different psychiatric clinical settings (emergency, inpatient, and outpatient services). Despite its usefulness, TDM remains underemployed in mental health. This is partly due to the need for evidence about the relationship between drug serum concentration and efficacy and tolerability, both in the general population and even more in subpopulations with atypical pharmacokinetics. This work aims at reviewing the scientific literature published after 2017, when the most recent guidelines about the use of TDM in mental health were written. We found 164 pertinent records that we included in the review. Some promising studies highlighted the possibility of correlating early drug serum concentration and clinical efficacy and safety, especially for antipsychotics, potentially enabling clinicians to make decisions on early laboratory findings and not proceeding by trial and error. About populations with pharmacokinetic peculiarities, the latest studies confirmed very common alterations in drug blood levels in pregnant women, generally with a progressive decrease over pregnancy and a very relevant dose-adjusted concentration increase in the elderly. For adolescents also, several drugs result in having different dose-related concentration values compared to adults. These findings stress the recommendation to use TDM in these populations to ensure a safe and effective treatment. Moreover, the integration of TDM with pharmacogenetic analyses may allow clinicians to adopt precise treatments, addressing therapy on an individual pharmacometabolic basis. Mini-invasive TDM procedures that may be easily performed at home or in a point-of-care are very promising and may represent a turning point toward an extensive real-world TDM application. Although the highlighted recent evidence, research efforts have to be carried on: further studies, especially prospective and fixed-dose, are needed to replicate present findings and provide clearer knowledge on relationships between dose, serum concentration, and efficacy/safety.

Practical Psychopharmacology: Using a Knowledge of Pharmacokinetics to More Rapidly Stabilize Patients at Lower Drug Doses.

Three drug dosing strategies can be employed to address dose-dependent drug adverse effects. The usual strategy is to continue the drug but at a lower dose; it would then take 5 half-lives of the drug for the new steady state to be attained and for a dose-dependent adverse effect to correspondingly attenuate. Such slow offset of the adverse effect could be disadvantageous for drugs such as fluoxetine, penfluridol, and cariprazine that have long half-lives. A second strategy is to stop the drug and to resume it at a lower dose when the adverse effect attenuates as the drug blood level falls. This strategy introduces subjectivity in timing the reintroduction of the drug, requires closer patient monitoring, and risks nonadherence and relapse. The third strategy is to stop the drug for a prespecified number of days and to then reintroduce it at a lower dose. From a knowledge of pharmacokinetics, it can be shown that stopping a drug for just 1 half-life and then resuming it at half the dose results in the immediate achievement of steady state; that is, there is no need to wait for 4 additional half-lives as with the usual strategy of dose reduction without dosing interruption. A limitation of this pharmacokinetically driven dosing strategy, however, is that it would work well in the average patient but not in those with outlying pharmacokinetic parameters.

First-in-Human Detection of Romiplostim Drug Levels in Cord Blood, Breastmilk and Blood in a Woman with ITP and Her Newborn Infant

First-in-Human Detection of Romiplostim Drug Levels in Cord Blood, Breastmilk and Blood in a Woman with ITP and Her Newborn Infant

Investigation of the relationship of frontal QRS-T angle and digoxin use and blood digoxin level

Objectives: Digoxin is an antiarrhythmic drug with a narrow therapeutic range and used in clinical conditions such as heart failure and atrial fibrillation. The planar frontal QRS-T angle reflects the deviations between the depolarization and repolarization of the ventricles, and it has been reported that an increase in this angle is associated with an increase in mortality. In our study, the relationship between frontal QRS-T angle and digoxin use and blood digoxin level was investigated. Methods: The study included 105 digoxin users who used digoxin, whose levels were measured, who had an electrocardiogram (ECG) on the system, and 15 patients with similar characteristics, who had an ECG and did not use digoxin. Patients using digoxin and whose levels were measured were also divided into three groups as &amp;lt; 0.8 ng/mL, 0.8-1.2 ng/mL, and &amp;gt; 1.2 ng/mL. The absolute value of the value obtained by subtracting the axis of the T wave from the axis of the QRS angle indicated on the paper, calculated automatically on the 12-lead ECG, was accepted as the frontal QRS-T angle value. Results: Planar frontal QRS-T angle measured by 12-lead ECG in digoxin users was 120º (55.5º-155.5º), while it was 106º (32º-163º) in non-users, and there was no statistical difference between the two groups (p = 0.833). In the evaluation made according to different blood drug levels as &amp;lt; 0.8 ng/mL, 0.8-1.2 ng/mL, &amp;gt; 1.2 ng/mL in digoxin users, no significant difference was observed between the frontal QRS-T angle between the groups (109.5° [60.25°-154.25°] for &amp;lt; 0.8 ng/mL, 136.5° [48.5°-158.5°] for 0.8-1.2 ng/mL, 117° [34°-154°] for 1.2 ng/mL) (p = 0.773).Conclusions: There was no significant difference in frontal QRS-T angle between digoxin users and non-users. There was no significant relationship between different blood digoxin levels and frontal QRS-T angle.

Ustekinumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum

BackgroundPatients with ulcerative colitis (UC) may be concerned about medication safety during preconception, pregnancy, and lactation, and they should be closely followed up to ensure that UC activity is controlled during the perinatal period. Reported information on the safety of ustekinumab during pregnancy and lactation is limited. In this case report, we examined the safety of ustekinumab in a fetus and breastfed infant with reference to drug concentrations in maternal serum, cord blood, breast milk, and infant serum.Case presentationA 36-year-old female who developed hematochezia and was diagnosed with ulcerative colitis at age 24 was pregnant with her first child. During pregnancy she was treated with subcutaneous bimonthly ustekinumab, at a dose of 90 mg, until 29 weeks of gestation. Her ulcerative colitis symptoms remained in remission. At 38 weeks of gestation she underwent cesarean section and delivered a healthy female infant weighing 3043 g and with no congenital malformations. The infant received routine vaccinations with no adverse events. Ustekinumab treatment was resumed at 7 weeks postpartum.The ustekinumab concentration in maternal serum at 12 days after injection (30.7 weeks of gestation) was 7968.5 ng/mL, and it decreased to 106.1 ng/mL at 114 days after the last dose. In cord blood, the ustekinumab concentration was 1131.2 ng/mL at 65 days after the last dose; this was 2.5 times higher than that in the maternal serum, which was consistent with a previous report. Ustekinumab was detected in infant serum collected at 71 days after the last maternal dose (299.0 ng/mL), with rapid elimination from the infant’s body. In breast milk, the maximum ustekinumab concentrations were 13.6 ng/mL at 9 days after the last maternal dose, respectively. The ratio of the calculated areas under the time-concentration curves of ustekinumab in breast milk and maternal serum was 0.0008 (257.1/327632.7), which was comparable with a previous human study.ConclusionThe placental transfer and breast milk secretion of ustekinumab in our case were comparable with previous reports. Use of ustekinumab during pregnancy and lactation was feasible in this case. Further research is needed to clarify the safety of ustekinumab during pregnancy and lactation.

RESISTANT HYPERTENSION IMPROVED AFTER 3 AND 6 MONTHS BY MEASURING DRUG LEVELS TO IDENTIFY NON-ADHERENCE

Objective: Identification of non-adherence to antihypertensive drugs is crucial to improve resistant hypertension (RH). For this measuring drug levels is the most reliable method. The primary objective of this analysis is to determine whether drug levels measured with a dried blood spot (DBS) sampling method combined with personalized feedback leads to a decrease in prevalence of RH after 3 and 6 months due to an increase in adherence. Design and method: This is a multi-center single-blinded randomized controlled trial (RHYME-RCT, NL6736). Patients went to an eligibility visit, where DBS sampling and a 24-hour ambulatory blood pressure measurement (ABPM) was performed simultaneously. Patients with a daytime systolic blood pressure (SBP) &gt; 135 and/or diastolic blood pressure (DBP) &gt; 85 mmHg were randomized to standard treatment (control) or intervention. The intervention was performed by the treating physician and included information on drug levels and a personalized feedback conversation based on a feedback tool. The follow-up period was one year and included visits at 3, 6 and 12 months after the eligibility visit. At each visit an ABPM and DBS were performed. Results: A total of 78 patients (mean age of 59 ± 11 years, 75.6% male) with at least six months of follow-up were included. The prevalence of RH decreased from 100% in both arms to 60.0% in the intervention arm (p &lt; 0.001, n = 35) and 58.1% in the control arm (p &lt; 0.001, n = 43) after 6 months of follow-up. Adherence rates also improved over time, but only significantly improved in the intervention group after 3 months (p = 0.020). Furthermore, no statistically significant differences were found after six months between the two groups in the degree of RH (p = 0.868), SBP (p = 0.759) or adherence (p = 0.841). Conclusions: Measuring blood pressure and drug levels led to a decrease in the prevalence of RH. However, this improvement could not be linked to the actual intervention or improvement of adherence. Note: In June 2022 data from the 12 months follow-up will also be complete and presented.

Imatinib alleviates lung injury and prolongs survival in ventilated rats.

Imatinib, a tyrosine kinase inhibitor, attenuates pulmonary edema and inflammation in lung injury. However, the physiological effects of this drug and their impact on outcomes are poorly characterized. Using serial computed tomography (CT), we tested the hypothesis that imatinib reduces injury severity and improves survival in ventilated rats. Hydrochloric acid (HCl) was instilled in the trachea (pH 1.5, 2.5 mL/kg) of anesthetized, intubated supine rats. Animals were randomized (n = 17 each group) to receive intraperitoneal imatinib or vehicle immediately prior to HCl. All rats then received mechanical ventilation. CT was performed hourly for 4 h. Images were quantitatively analyzed to assess the progression of radiological abnormalities. Injury severity was confirmed via hourly blood gases, serum biomarkers, bronchoalveolar lavage (BAL), and histopathology. Serial blood drug levels were measured in a subset of rats. Imatinib reduced mortality while delaying functional and radiological injury progression: out of 17 rats per condition, 2 control vs. 8 imatinib-treated rats survived until the end of the experiment (P = 0.02). Imatinib attenuated edema after lung injury (P < 0.05), and survival time in both groups was negatively correlated with increased lung mass (R2 = 0.70) as well as other physiological and CT parameters. Capillary leak (BAL protein concentration) was significantly lower in the treated group (P = 0.04). Peak drug concentration was reached after 70 min, and the drug half-life was 150 min. Imatinib decreased both mortality and lung injury severity in mechanically ventilated rats. Pharmacological inhibition of edema could be used during mechanical ventilation to improve the severity and outcome of lung injury.

Whole blood drug levels do not correlate with QTc intervals in hydroxychloroquine-treated systemic lupus erythematosus patients.

ObjectivesHCQ is recommended for all patients with SLE, but reports of cardiac toxicity in severe acute respiratory syndrome coronavirus 2 patients raised concerns. We aimed to study the relationship between HCQ blood levels and QTc intervals.MethodsA retrospective review of 90 SLE patients (cohort 1) was conducted with data collected regarding demographics, QTc interval and chronic kidney disease (CKD). A prospective study of 84 SLE patients (cohort 2) was conducted with data collected regarding demographics, dose of HCQ, duration of HCQ treatment, presence of echocardiographic abnormalities and CKD simultaneous with whole blood HCQ levels measured by HPLC. Statistical analysis utilized one-way analysis of variance, Pearson’s correlation coefficient and t tests.ResultsIn cohort 1 there was no significant difference in mean QTc based on 75 HCQ-treated [437.91 msec (s.d. 20.02)] as compared with 15 untreated patients [434.6 msec (s.d. 27.49)]. In patients with CKD, the mean QTc in HCQ users [448 (s.d. 23.37)] as compared with non-users [444.5 msec (s.d. 24.61)] also had no significant difference. In cohort 2, HCQ levels did not correlate with QTc interval (r = 0.017) and this applied regardless of the dose prescribed (r = 0.113 for 400 mg and r = 0.06 for 200 mg), duration of exposure (P = 0.36 for 0–5, >5–10 or >10 years), CKD (r = 0.482) or underlying cardiac abnormalities (r = 0.430).ConclusionsThis is the first study relying on measured blood levels demonstrating the absence of a clinically consequential increase in QTc levels in HCQ-treated SLE patients.

Novel Tablet Dosage Forms to Improve the Oral Bioavailability of Curcumin: A Short Review

AbstractCurcumin is a yellow pigment that is considered as the major biologically active compound of turmeric plant. Curcumin has antioxidant, anti-inflammatory, anti-microbial, anti-neoplastic, and anti-depressant properties. However, due to poor oral bioavailability, its applications has been largely hampered in the clinical settings. Currently, advances in curcumin formulations to different dosage forms such as tablets, capsules or semisolid preparations have been resulted in solving its poor oral bioavailability and subsequently increasing the blood levels of drug for therapeutic activity. In this article, the ongoing researches of formulation of curcumin into different dosage forms that have been used to improve its oral bioavailability has reviewed. In particular, we have focused on formulation of curcumin into tablet dosage forms because the tablet is the most popular type of dosage form for the patients.

Therapeutic drug monitoring in epilepsy: Can drug levels reliably measure drug adherence?

Background: Drug adherence is often assessed from patients' reports and confifirmed with therapeutic drug monitoring. The study investigated the relationship between reports of drug adherence and drug levels of carbamazepine among adult patients on carbamazepine monotherapy. Methods: 84 consecutively consenting patients who had been on carbamazepine monotherapy for seizure control were recruited from the Neurology Clinic, LUTH, Idi-Araba, Lagos for the study. Adherence in the past month was assessed using a standard proforma. Drug levels were taken in the trough phase (just before the next dose of carbamazepine) and analyzed using high performance liquid chromatography. Results: Among the population studied, full adherence was reported in 45.2% of the participants while the remainder had missed one or more doses in the past month. Serum drug levels were found to be signifificantly higher in patient who reported full adherence compared to non-adherent patients (p&lt;0.05). When levels were compared to the reference range of carbamazepine, 15.8% of the patient who reported good adherence had blood levels in the subtherapeutic range, while 21.7% who reported poor adherence had blood levels in the subtherapeutic range (p&gt;0.05). Conclusion: Adherence is associated with higher drug levels, but both adherent and nonadherent patients had a similar likelihood of having serum drug blood levels in the subtherapeutic range. This calls for caution in the interpretation of drug levels as it relates to adherence. Further studies on standardization of therapeutic drug measurement to develop predictive tools for adherence are recommended.

A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities.

Wu Wei Zi is the dried fruit of Schisandra chinensis (Turcz.) Baill. or Schisandra sphenanthera Rehd. et Wils. (family Magnoliaceae). As a homology of medicine and food, it has been widely used in China for thousands of years, to tonify the kidney, and ameliorate neurological, cardiovascular, liver, and gastrointestinal disorders. As its increasing health benefits and pharmacological value, many literatures have reported that the combination of Wu Wei Zi in patients has led to fluctuations in the blood level of the combined drug. Therefore, it is extremely important to evaluate its safety concern such as drug-drug interactions (DDIs) when patients are under the poly-therapeutic conditions. This review summarized the effects of Wu Wei Zi extract and its major lignan components on cytochrome P450 and P-glycoprotein activities, the change of which could induce metabolic DDIs. Our review also elaborated on the differences of the major lignan components of the two Schisandra species, as well as the absorption, distribution, metabolism, and elimination of the major lignans. In conclusion, these results would enhance our understanding of the DDI mechanisms involving Wu Wei Zi, and may potentially untangle some differing and conflicting results in the future.