Monitoring Of Serum Concentrations Research Articles

Intraoperative PTH monitoring: a new approach based on the identification of the “true” time origin of the decay curve

Some published criteria for intraoperative monitoring of PTH serum concentrations may cause misleading results, since the timing of samples measured between the pre-incision and pre-excision phase of surgery is often unrecorded. In our opinion this information is critical, as the time of an intermediate sample during surgical manipulation may represent the "true" beginning of the PTH decay. We modified the usual criterion of monitoring (cut-off at 10 minutes after clamping) proposing a further check at manipulation in case the primary check at clamping produces an apparently negative result. On the basis of a mathematical model, false negative curves were simulated by means of a time shift. This shift was assumed to be the interval between manipulation and clamping. Analysing the decay curve, we used the 50% cut-off at 10 minutes after the supposed "true" origin (clamping or manipulation). Using a rapid immunochemiluminometric assay (ICMA), data were collected from 22 patients successfully operated for parathyroid adenoma. The check at clamping correctly diagnosed 13 patients. Among the 9 false negative cases, 6 were correctly diagnosed considering the manipulation as the baseline value. In the remaining 3 patients, diagnosis required prolonged observation of the curves. In case the iPTH decay does not follow the expected curve, it can be useful to check the decay normalising to a pre-excision value. The advantages of our criterion are both the prompt recognition of false negative results and the construction of a "true" decay curve for each patient, supporting the surgeon during the excision of hyperfunctioning parathyroid tissue.

Analysis of serum concentrations of anti-epilepsy drugs in 113 case-times

Objective To provide some references for clinical individualized mediaction analyzing the serum concentrations of anti-epilepsy drugs.Methods Enzyme-mutiplied immunoassay technique (EMIT)was used to determine the sermn concentrations of anti-epilepsy drugs in 113 case-times,then the concentrations were analyzed and compared with SPSS 16.0.The impact of age,sex,and drug combination on the serum concentrations of anti-epilepsy drugs and the relation between the serum concentrations of antiepilepsy drugs and therapeutic effect were analyzed.Results Among the serum concentrations of carbamazepine in 24 case-times,2 case-times whose diseases were totally controlled were lower than 4 μ g/ml;19 case-times between 4 and 12 μ g/ml,with an effective rate of 78.95％;3 case-times higher than 12 μ g/ml,with an effective rate of 66.67％.Among the serum concentrations of valproic acid in 74 case-times,24 case-times were lower than 50 μ g/ml,with an effective rate of 79.17％;43 case-times between 50 and 100 μ g/ml,with an effective rate of 81.40％;7 case-times higher than 100 μ g/ml,with an effective rate of 71.43％.Drug combination with carbamazepine had 13 case-times;61.54％ of the serum concentrations were within the effective range.Drug combination with valproic acid had 12 case-times;16.67％ of the serum concentrations were within the effective range.The impact of age,sex,and drug combination on the serum concentrations of anti-epilepsy drugs and the relation between serum concentration and therapeutic effect had no difference in statistics.Conclusions There are great individual differences among patients in the serum concentrations of antiepilepsy drugs.It is unilateral to adjust the dosage of drugs only depending on serum concentration.In clinical treatment,the serum concentrations of anti-epilepsy drugs are only references for adjusting drug dosage.We should adjust the drug dosage in term of the patients' conditions and the serum concentration of drug so that the patients will get the best therapeutic effect with a smallest drug dosage. Key words: Anti-epilepsy drugs; Serum concentration monitoring; Carbamazepine; Valproic acid

Influence of plasma exchange on rituximab pharmacokinetics

Rituximab, an anti CD20 monoclonal antibody is approved for the treatment of B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukaemia and rheumatoid arthritis [1]. It is also used off label for the treatment of lymphomas induced by the Epstein–Barr virus (EBV) after bone marrow or organ transplant [2], in particular forms of organ transplant rejection (acute humoral rejection) [3] and in a number of autoimmune diseases. Plasma exchange (PEx) is an extracorporeal blood purification technique allowing the removal of large molecular weight substances from the plasma and hence is used in various diseases including cryoglobulinaemia. In this last condition, its aim is to eliminate pathogenic antibodies involved in vascular and glomerular lesions. Because PEx is not selective, it also leads to the elimination of any circulating therapeutic antibody. An impact of PEx on plasma concentrations of basiliximab and rituximab [4, 5] was reported but its influence of monoclonal antibody pharmacokinetics was not studied. We report the use of compartmental pharmacokinetic modelling to quantify the impact of multiple PEx sessions on exposure to rituximab in two patients. Two patients with non-Hodgkin's lymphoma (MALT-type lymphoma and lymphoma following liver transplantation) treated with rituximab underwent multisession PEx for cryoglobulinaemia associated with membranoproliferative glomerulonephritis. Rituximab was administered intravenously at a dose of 350 mg m−2 weekly for 4 weeks to a 49 kg, 52-year-old woman (patient 1) and as six injections of 375 mg m−2 over 6 months to a 80 kg, 56-year-old man (patient 2). Patient 1 underwent weekly plasmapheresis sessions. Patient 2 underwent plasmapheresis twice a month during rituximab treatment, followed by weekly sessions. In both cases, plasmapheresis sessions were performed before rituximab injections, except for one plasmapheresis session (patient 1), performed 14 h after the infusion. Blood samples were collected 2 h after rituximab injections and before, immediately and 6 h after plasmapheresis sessions, in accordance with the policy of the local Ethics Committee. Serum rituximab concentrations were measured by enzyme-linked immunosorbent assay [6] and rituximab pharmacokinetics were described using a two compartment model with two elimination clearances, a ‘physiological’ clearance (CL) and a ‘PEx’ clearance (CLP) taking place only during the sessions. Estimated parameters were 0.2 and 0.5 l day−1 for CL, 28 and 20 l day−1 for CLP, 1.9 and 3.2 l for central compartment volume, 3.2 and 3.3 l for peripheral compartment volume and 5.2 and 4.5 l day−1 for intercompartment clearance, for patients 1 and 2, respectively. The model was used to simulate cumulated rituximab areas under the concentration vs. time curves (AUC) with and without plasmapheresis (Figure 1). This simulation showed a decrease in exposure to rituximab of 38% at day 54 and 10% at day 274 for patients 1 and 2, respectively (Figure 1). Figure 1 Observed (circles), model-predicted rituximab serum concentrations (black lines) and cumulated AUC (grey lines) as a function of time in the two patients. Predicted concentrations and cumulated AUC (* – dashed lines) in the absence of PEx (without ... Our model is the first to describe the pharmacokinetics of rituximab when it is associated with PEx. This procedure had a marked impact on patients' exposure to rituximab. The pharmacokinetic model may also be used to predict the consequences of alterations in rituximab dose or in interval between infusion and PEx. However, the pharmacokinetic consequences of PEx can be minimized by applying PEx sessions at the end of dosing intervals. Alternatively, patients given repeated infusions of rituximab in association with PEx may benefit from an individual dose adjustment based on the monitoring of rituximab serum concentrations.

Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy

The aims of the study were to characterize the magnitude of clearance changes during pregnancy for multiple antiepileptic drugs (AEDs) and to assess seizure frequency and factors increasing seizure risk in pregnant women with epilepsy. A retrospective analysis was performed for 115 pregnancies in 95 women with epilepsy followed at the Emory Epilepsy Center between 1999 and 2012. Antiepileptic drug blood levels (ABLs) obtained during routine clinical practice were used to calculate AED clearance at multiple points during pregnancy. Antiepileptic drug doses and seizure activity were also recorded. The data were analyzed for changes in clearance and dose across pregnancy and for an association between ABL and changes in seizure frequency. Significant changes in clearance during pregnancy were observed for lamotrigine (p<0.001) and levetiracetam (p<0.006). Average peak clearance increased by 191% for lamotrigine and 207% for levetiracetam from nonpregnant baseline. Marked variance was present across individual women and also across repeat pregnancies in individual women. Despite increased AED dose across most AEDs, seizures increased in 38.4% of patients during pregnancy. Seizure deterioration was significantly more likely in patients with seizures in the 12months prior to conception (p<0.001) and those with localization-related epilepsy (p=0.005). When ABL fell >35% from preconception baseline, seizures worsened significantly during the second trimester when controlling for seizure occurrence in the year prior to conception. Substantial pharmacokinetic changes during pregnancy occur with multiple AEDs and may increase seizure risk. Monitoring of AED serum concentrations with dose adjustment is recommended in pregnant women with epilepsy. Further studies are needed for many AEDs.

Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome

SummaryBackgroundHuman infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China.MethodsBetween March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentrations of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples. We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes.FindingsWe identified four patients (mean age 56 years), all of whom had contact with poultry 3–8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. Two patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs. The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affinity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2.InterpretationCross species poultry-to-person transmission of this new reassortant H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness.FundingLarry Chi-Kin Yung, National Key Program for Infectious Diseases of China.

Antiepileptic drug treatment in pregnancy: Changes in drug disposition and their clinical implications

Pregnancy is a state where pharmacokinetic changes are more pronounced and more rapid than during any other period of life. The consequences of such changes can be far reaching, not least in the management of epilepsy where the risks with uncontrolled seizures during pregnancy need to be balanced against potential teratogenic effects of antiepileptic drugs (AEDs). This article aims to review the literature on gestational effects on the pharmacokinetics of older and newer generation AEDs and discuss the implications for the treatment of epilepsy in women during pregnancy. Pregnancy can affect the pharmacokinetics of AEDs at any level from absorption, distribution, metabolism, to elimination. The effect varies depending on the type of AED. The most pronounced decline in serum concentrations is seen for AEDs that are eliminated by glucuronidation (UGT), in particular lamotrigine where the effect may be profound. Serum concentrations of AEDs that are cleared mainly through the kidneys, for example, levetiracetam, can also decline significantly. Some AEDs, such as carbamazepine seem to be affected only marginally by pregnancy. Data on pharmacokinetics during pregnancy are lacking completely for some of the newer generation AEDs: pregabalin, lacosamide, retigabine, and eslicarbazepine acetate. Where data are available, the effects of pregnancy on serum concentrations seem to vary considerably individually and are thus difficult to predict. Although large-scale systematic studies of the clinical relevance of the pharmacokinetic alterations are lacking, prospective and retrospective case series have reported an association between declining serum concentrations and deterioration in seizures control. The usefulness of routine monitoring of AED serum concentrations in pregnancy and of dose adjustments based on falling levels, are discussed in this review. We suggest that monitoring could be important, in particular when women have been titrated to the lowest effective AED dose and serum concentration before pregnancy, and when that individual optimal concentration can be used as reference.

ジフェンヒドラミン含有軟膏の大量誤飲で急性薬物中毒に至った症例の血中濃度モニタリング

急性薬物中毒患者が搬入された際には,薬剤師が中毒原因物質に関する情報を迅速に収集し,個々の症例にあった適切な情報と治療方法を医師,看護師に提案する必要がある。 今回,ジフェンヒドラミン(以下,DPH)含有軟膏を大量に誤飲した99歳女性の救命治療に対して,胃洗浄を含めた治療方法と,患者の血中DPH濃度を経時的に測定することを提案した。その結果,血中DPH濃度の低下とともに臨床症状の改善が認められ,DPH含有軟膏誤飲例に対して胃洗浄を施行したこと,および血中濃度測定の臨床における有用性が示唆された。

Rational use of aminoglycosides—Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)

The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

Dosing and Monitoring of Methadone in Pregnancy: Literature Review

The pharmacokinetics of methadone is altered during pregnancy, but the most appropriate dosing and monitoring regimen has yet to be identified. To review dosing and monitoring of methadone therapy in pregnancy. A literature search was performed in several databases (PubMed, MEDLINE, Embase, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews) from inception to May 2012. The search terms were "methadone", "pregnancy", "pharmacokinetic", "clearance", "metabolism", "therapeutic drug monitoring", and "methadone dosing". Additional papers were identified by searching the bibliographies of primary and review articles. All English-language primary articles related to methadone pharmacokinetics in pregnancy were included. Articles not related to maternal outcomes were excluded. The literature search yielded 1 case report and 10 studies discussing use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has been studied in 3 pharmacokinetic trials, and split dosing of methadone in pregnant women has been described in 1 case report and 3 dosing trials. Only 4 trials evaluated monitoring of methadone concentration in pregnancy. The studies included in this review confirm that methadone pharmacokinetics is altered in pregnancy and is potentially correlated with increases in maternal withdrawal symptoms. Insufficient evidence is available to warrant routine monitoring of serum methadone concentrations in pregnant women with opioid dependence. Few studies of methadone pharmacokinetics and therapeutic drug monitoring are available for pregnant women with opioid dependence. Although it is known that methadone pharmacokinetics is altered in pregnancy, there is insufficient evidence to guide dosage adjustments and serum concentration monitoring. Until further studies are available, regular follow-up of maternal withdrawal symptoms and empiric dosage adjustments throughout pregnancy are still recommended.

Use of 4-mg/kg/24-Hour Empiric Aminoglycoside dosing in Preoperative Neonates with Congenital Heart Disease

Empiric dosing of gentamicin has not been evaluated in critically ill neonates with unrepaired congenital heart disease (CHD). Many factors may alter gentamicin pharmacokinetics in this patient population and there are few data describing gentamicin dosing regimens in this patient population. To determine whether an empiric gentamicin dosing regimen for neonates achieves acceptable serum trough concentrations in neonatal patients with unrepaired CHD receiving alprostadil. Term neonates with unrepaired CHD who received gentamicin for empiric treatment of sepsis were identified over a 3-year period. Patients were included if they received gentamicin 4 mg/kg/dose every 24 hours, were receiving alprostadil for maintenance of a patent ductus arteriosus, and had at least one gentamicin serum trough concentration determined. Patients were evaluated to determine whether they achieved a serum trough concentration of <1 mg/L, and differences in patient characteristics were noted for those who achieved an appropriate trough concentration and those who did not. Twenty-eight patients met study criteria, and 22% of patients had a trough gentamicin concentration of <1 mg/L at a mean (SD) time of 23.6 (0.3) hours after a dose. Few statistically significant differences in patient characteristics were noted for those who achieved an appropriate serum trough concentration and those who did not, and included Apgar scores at 1 minute and later day of life at admission. Current empiric gentamicin dosing regimens may not be appropriate for critically ill neonates with unrepaired CHD. Routine serum concentration monitoring may be warranted in this population.

Pharmacokinetic simulation of fatal carbamazepine intoxication in 23-month old child following phenytoin discontinuation

The antiepileptic, carbamazepine, is extensively metabolized via hepatic enzymes in the cytochrome P450 family and is therefore subject to a myriad of drug interactions. Concomitant administration with phenytoin enhances carbamazepine metabolism thus reducing serum concentrations and necessitating the use of a higher maintenance dose. Removal of phenytoin therapy in the absence of anticipatory dose adjustments and careful monitoring of serum concentrations may result in catastrophic outcomes. Reported herein are the events leading to the death of a 23-month old child who suffered a fatal carbamazepine overdose following withdrawal of phenytoin therapy.

Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: The diagnostic significance of interleukin-18 and interleukin-6

Macrophage-activation syndrome (MAS) is a potentially life-threatening complication of systemic juvenile idiopathic arthritis (s-JIA). Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, is an effective cytokine inhibitor for the treatment of s-JIA. We described the clinical courses of five cases of MAS during TCZ therapy and demonstrated the need for monitoring serum interleukin (IL)-18 and IL-6 concentrations. Clinical symptoms of patients with s-JIA receiving TCZ were apparently mild compared to those not receiving TCZ. Furthermore, serum CRP concentrations never increased during TCZ therapy, even in MAS. Serum IL-6 concentrations increased during s-JIA flare-up and with the complication of infection. Serum IL-18 concentrations increased persistently before the other measures of disease activity. The clinical symptoms of MAS and s-JIA could be masked during TCZ therapy; hence, monitoring serum concentrations of IL-18 and IL-6 is recommended for the evaluation of disease activity in s-JIA and to detect the complication of infection.

Vancomycin utilization evaluation at hematology-oncology ward of a teaching hospital in iran.

The aim of the present study was to evaluate the pattern of vancomycin administration in the hematology-oncology ward of Nemazee Hospital, Shiraz, Iran. Study criteria were developed to assess the several parameters involved in vancomycin therapy. These parameters include the appropriateness of drug usage, dosage, duration of therapy, monitoring for toxicity and serum concentration monitoring. The serum concentration was measured by an automated Fluorescence Polarization Immunoassay. Clinical and preclinical parameters such as Glomerular Filtration Rate (GFR), microbial culture, antibacterial sensitivity, WBC count and fever were collected and recorded for analysis. Sixty patients were enrolled in the study, consisting of 45 males and 15 females. The age range was 15 to 68 years. In this study, 68.63% of the vancomycin used for the patients with febrile neutropenia was compatible with the Infectious Disease Society of America (IDSA) guideline. The initial dosage of vancomycin in 68.63%, rate of infusion in 100%, and dilution of vancomycin in100%, were appropriate. Inappropriate use was more evident in the continuation of vancomycin in 50% of the patients. No appropriate dosage adjustment was done for 50% of the patients with increased serum creatinine. Based on the results, the indication of vancomycin in febrile neutropenia was satisfactory. However, there were some required factors such as continuation of vancomycin, adjustment of dosage or interval, microbial culture, antibiotic sensitivity test before the first dose administration, measurement of serum concentration and monitoring which had to be revised in order to achieve an effective treatment.

Analysis of the valproic acid-meropenem interaction in hospitalised patients

IntroductionPublished data demonstrate a serious interaction between valproic acid and meropenem. However, recommendations about the management of concomitant treatment are contradictory; some experts recommend closer monitoring of valproic acid serum concentrations and others recommend avoiding concurrent therapy. The purpose of this study is to critically analyse the interaction and to evaluate the impact of pharmaceutical intervention in the use of these drugs in hospitalised patients. Material and methodsStudy of the concomitant prescription of valproic acid and meropenem in a general hospital of 1080 beds divided in to two periods; the first period was retrospective and observational and it was followed by a prospective period involving pharmaceutical intervention. The prescription habits between both periods were compared. ResultsA total of 26 patients received concurrent treatment with valproic acid and meropenem (13 per period) and none of them maintained therapeutic serum levels of the antiepileptic drug. Pharmaceutical intervention modified prescription habits, reducing by half the number of days of concomitant treatment, changing the antibiotherapy and/or monitoring serum concentrations more often. ConclusionsThe interaction between valproic acid and meropenem is serious, especially because of the dramatic decrease in the antiepileptic serum concentrations. The concomitant use of both drugs should be avoided, replacing the antibiotherapy empirically, or according to the resistance profiles of the microorganism and maintaining the same the anti-epileptic treatment.

Analysis of related factors between the serum concentrations of sodium valproate and its effectiveness

Objective: To analyze the influencial factors of serum concentrations of sodium valproate in epilepsy patients,so as to provide reference for rational use of sodium valproate.Methods: Serum concentrations of sodium valproate were determined by enzyme-enhancement immunoassay technique.The relationships of serum concentrations of sodium valproate,age and gender of patients,therapeutic effectiveness and dosages were analyzed.Results: In the 158 cases,the concentrations of sodium valproate which were 50,50-100,100 μg/ml accounted for 69(43.67%),70(44.30%),19(12.03%) and the total effective rates were 36.32%,87.14%,78.94%,respectively.The effectiveness were significantly different among different serum concentration groups(50,50-100,100 μg/ml),and different dose groups(400,400-800,800 mg/d).There was no statistical difference between male and female patients,or among different age groups.Conclusion: It is necessary to make out individual therapeutic regimens of sodium valproate according to results of serum concentration monitoring.

Reformulation of Current Recommendations for Target Serum Lithium Concentration According to Clinical Indication, Age and Physical Comorbidity

There have been significant changes in the nature of psychiatric patient populations and patterns of drug prescribing in mood disorders since serum lithium monitoring was introduced. It seems opportune to review current guidelines for target lithium concentration given the decline in lithium monotherapy and increase in the numbers of older people and those with comorbid physical disease administered lithium. A review was made of the literature of lithium monitoring and target serum concentration in mood disorders, older people, and comorbid physical illness. Current guidelines, which generally recommend a target serum concentration of 0.5/0.6 to 1.1/1.2 mmol/L, have a number of limitations. A target lithium level of > 0.8 mmol/L is inappropriate given poor tolerability, and adequate efficacy when combination lithium-antipsychotic therapy is used at this or lower levels. Guidelines have largely failed to match specific clinical indications to serum levels, and to consider comorbid physical illness factors known to be associated with lithium toxicity. For most patients, a target serum lithium concentration range of 0.5-0.8 mmol/L, varying according to clinical indication, age and concurrent physical status, seems most appropriate in enhancing efficacy and minimizing adverse effects. The lower end of this range (0.5-0.6 mmol/L) is recommended for patients 50 years and over; those with diabetes insipidus, renal impairment or thyroid dysfunction; those administered diuretics, angiotensin converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors; and in the prophylaxis of bipolar depression and management of acute unipolar depression. The higher end of this range (0.7-0.8 mmol/L) is recommended in the management of acute mania and prophylaxis of mania.

Methanol Ingestion

Methanol Ingestion

Evaluation of the Accuracy of a Pharmacokinetic Dosing Program in Predicting Serum Vancomycin Concentrations in Critically III Patients

Optimization of the timing of appropriate antibiotics is crucial to improve the management of patients in severe sepsis and septic shock. Vancomycin is commonly used empirically in cases of nosocomial infections in critically ill patients. Therefore, early optimization of vancomycin pharmacokinetics is likely to improve outcomes. To evaluate a pharmacokinetic program to predict serum vancomycin concentrations in accordance with administered dose, weight, height, and creatinine clearance in a critically ill population. We conducted a prospective observational single-center study in a 45-bed intensive care unit (ICU). All patients hospitalized in the ICU requiring intravenous treatment with vancomycin for a suspected infection were enrolled. The modalities of vancomycin therapy and the monitoring of serum concentrations were left to the discretion of the treating clinician. We compared the measured serum vancomycin concentrations with those predicted by the MM-USCPACK program and analyzed the factors influencing the prediction. Fifty-four intravenous vancomycin courses were administered in 48 critically ill patients over the 3-month study. The precision was considered acceptable, based on a relative precision equal to 8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed concentrations; factors correlating with a poorer prediction were a change in renal function, obesity, and the magnitude of organ dysfunction on initiation of vancomycin (expressed by a Systemic Organ Failure Assessment score >11). The MM-USCPACK program is a useful and reliable tool for prediction of serum vancomycin concentrations in patients hospitalized in ICU and likely reflects the close monitoring of renal function in this setting. For some patients (more severely ill, obese, or significant change in renal function during vancomycin therapy), predictions were less precise.

National Survey of Extended-Interval Aminoglycoside Dosing in Pediatric Cystic Fibrosis Pulmonary Exacerbations

The Cystic Fibrosis Foundation recently deemed the use of extended-interval dosing (EID) of aminoglycosides acceptable for the treatment of cystic fibrosis (CF) pulmonary exacerbations, but current practices across United States (US) pediatric CF accredited care centers and affiliate programs are unknown. The objectives of this research are to characterize the practice trends, dosing strategies, therapeutic drug monitoring practices, and adverse drug reaction monitoring of EID of aminoglycosides in the treatment of pulmonary exacerbations across US pediatric CF programs. A 38-question online survey was distributed on behalf of the author by the CF Foundation to all US pediatric CF accredited care centers and affiliate programs. Of the 70 participating CF programs (42.2% survey response rate), 94.3% reported using EID of aminoglycosides (as once-daily or twice-daily dosing), whereas 84.3% reported using once-daily EID in their pediatric CF population. The frequency of EID use increased with patient age. Tobramycin dosed 10 mg/kg per day every 24 hours, infused over the course of 30 minutes, in combination with an antipseudomonal beta-lactam, was the most commonly cited regimen. Monitoring of aminoglycoside serum concentrations was reported by 98.5% of programs, with a tobramycin peak of 25 to 30 mg/L and trough of less than 1 mg/L targeted most frequently. Nephrotoxicity was commonly monitored through serum creatinine measurements, whereas ototoxicity was monitored by audiometry in approximately one-half of programs. This study indicates that the use of EID of aminoglycosides across US pediatric CF accredited care centers and affiliate programs is common, particularly among adolescents, with tobramycin being the preferred agent.

Evaluation of the Accuracy of a Pharmacokinetic Dosing Program in Predicting Serum Vancomycin Concentrations in Critically Ill Patients

Optimization of the timing of appropriate antibiotics is crucial to improve the management of patients in severe sepsis and septic shock. Vancomycin is commonly used empirically in cases of nosocomial infections in critically ill patients. Therefore, early optimization of vancomycin pharmacokinetics is likely to improve outcomes.To evaluate a pharmacokinetic program to predict serum vancomycin concentrations in accordance with administered dose, weight, height, and creatinine clearance in a critically ill population.We conducted a prospective observational single-center study in a 45-bed intensive care unit (ICU). All patients hospitalized in the ICU requiring intravenous treatment with vancomycin for a suspected infection were enrolled. The modalities of vancomycin therapy and the monitoring of serum concentrations were left to the discretion of the treating clinician. We compared the measured serum vancomycin concentrations with those predicted by the MM-USCPACK program and analyzed the factors influencing the prediction.Fifty-four intravenous vancomycin courses were administered in 48 critically ill patients over the 3-month study. The precision was considered acceptable, based on a relative precision equal to 8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed concentrations; factors correlating with a poorer prediction were a change in renal function, obesity, and the magnitude of organ dysfunction on initiation of vancomycin (expressed by a Systemic Organ Failure Assessment score >11).The MM-USCPACK program is a useful and reliable tool for prediction of serum vancomycin concentrations in patients hospitalized in ICU and likely reflects the close monitoring of renal function in this setting. For some patients (more severely ill, obese, or significant change in renal function during vancomycin therapy), predictions were less precise.