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PubMed2004

Therapeutic drug monitoring of cyclosporine.

The introduction of cyclosporine into clinical practice improved transplant outcome. However, the use of cyclosporine is not without problems. A narrow therapeutic index (the drug causes irreversible kidney damage when given in too high a dose) coupled with variable absorption and unpredictable pharmacokinetics has resulted in the need to measure cyclosporine blood concentrations to enable the dose of the drug to be individualised to the patient. When this is done correctly therapeutic efficacy can be maximised while toxicity is kept to a minimum. The evolution of cyclosporine dose optimisation started with the adjustment of empirical fixed doses by clinical "judgement;" progressed to therapeutic drug monitoring of trough, predose, C0 concentration with non specific assays that measured parent drug and metabolite; then on to "specific" cyclosporine C0 measurements; through area under curve monitoring using full profile measurements and limited sampling scheme procedures; and finally ending up with absorption profiling that targets AUC in the first 4 hours or the 2 hour blood cyclosporine concentration, C2. At the same time the formulation of cyclosporine has changed from Sandimmune to Neoral and now generic forms of the latter are available. The evidence base supporting C2 monitoring continues to grow and the technique will need to be customised as new combination therapies emerge. Therapeutic drug monitoring of cyclosporine may also need to be tailored to avoid the potential negative impact of switching patients to generic forms of the drug.

Area Under Curve↗
PubMed2004

Investigation of genotoxic effect of ultrasound in cases receiving therapeutic ultrasound by using micronucleus method.

In 1991, reported that therapeutic ultrasound (US) did not induce sister chromatid exchanges (SCEs) in patients whereas, in 1984, reported that each of 10 patients exposed to therapeutic US had a statistically significant increase in SCEs. The present study was planned to investigate if there was chromosomal damage resulting from therapeutic US by using a micronucleus (MN) method, and to counter the lack of reports in this area over the past 10 years. A total of 20 female volunteers were included in the study; 10 of them with low back pain (mechanical low back pain and facet syndrome) were treated with US and 10 healthy cases constituted the control group. Patients with low back pain received 10 sessions of US therapy at an intensity of 2 W/cm(2) and a frequency of 1 MHz for 10 min and patients in the control group received sham US therapy for 10 min. Peripheral blood taken before and after the fifth and tenth applications of US therapy was cultured for MN frequencies both for the treatment and the control groups. The scores of MN assessed before the therapy were compared with those at the end of the fifth session and the end of the tenth session in the treatment and the control groups. Pretreatment, end of the fifth session and end of the tenth session MN frequencies were compared between the treatment and the control groups. There was no statistically significant difference in MN frequencies between pretreatment and fifth session or pretreatment and tenth session in both groups. Nor was there any significant difference in the MN frequencies of the treatment and control groups between pretreatment, fifth session and tenth session evaluations. In conclusion, we observed that therapeutic US did not induce increases in MN frequency, which are a sign of cytogenetic damage.

Adult↗
PubMed2006

Will suburothelial injection of small dose of botulinum A toxin have similar therapeutic effects and less adverse events for refractory detrusor overactivity?

OBJECTIVES: To investigate whether suburothelial injection of different doses of botulinum A toxin (BTX-A) will have a similar therapeutic effect but fewer adverse events than 200 U BTX-A in patients with refractory detrusor overactivity. METHODS: A total of 75 patients with detrusor overactivity refractory to anticholinergics were enrolled and randomized to receive 100, 150, or 200 U of BTX-A injected into the suburothelial space at 40 sites. Urinary incontinence was graded on a self-reported scale of 0 to 3, representing continence and mild, moderate and severe incontinence, respectively. The therapeutic effects, adverse events, and urodynamic parameters were assessed at 3 months. RESULTS: An excellent result at 3 months was obtained in 34.8%, 36%, and 40.7% of patients treated with 100, 150, and 200 U of BTX-A, respectively. The patients who received 100 U of BTX-A had a lower incidence of a large postvoid residual urine volume (150 mL or more) than did those who received 150 or 200 U (30.4% versus 52% and 72%, respectively, P = 0.011) after treatment. The posttreatment urodynamic parameters were similar between the patients who received 150 or 200 U of BTX-A, but the changes in bladder capacity and postvoid residual urine volume were greater than those for the patients who received 100 U. The duration of therapeutic effectiveness was significantly shorter for the patients treated with 100 U compared with that for those treated with 150 or 200 U of BTX-A. CONCLUSIONS: Suburothelial injection of 100 U of BTX-A achieved a similar rate of excellent results and had significantly fewer adverse events compared with 150 or 200 U. The dose of suburothelial BTX-A also affected the duration of therapeutic effectiveness.

Botulinum Toxins, Type A↗
PubMed2004

A therapeutic HIV vaccine: how good is good enough?

The goal of a therapeutic HIV vaccine is to attenuate HIV disease progression in those already infected. Our objective was to establish comparative efficacy and cost-effectiveness thresholds at which a therapeutic vaccine would make a valuable contribution to HIV care. Using an HIV computer simulation model, we compared therapeutic vaccination with HIV standard of care without vaccination. Input data were obtained from the literature. Base case and sensitivity analyses related to vaccine magnitude, penetrance, durability, and cost. In the base case (0.5 log magnitude, 25% penetrance, 3-year durability, and US$ 4000 per series), vaccination increased quality-adjusted life expectancy (QALE) by 0.50 months compared to no vaccination (cost-effectiveness ratio US$ 89,900 per quality-adjusted life year (QALY)). Increasing vaccine penetrance to 50% increased the projected QALE benefit to 0.91 months (cost-effectiveness ratio US$ 45,500/QALY). Even modestly effective therapeutic HIV vaccines may produce small but meaningful increases in life expectancy and compare favorably to alternative uses of scarce HIV care resources.

AIDS Vaccines↗
PubMed2006

Gene therapy of the ischemic lower limb--Therapeutic angiogenesis.

The limitations of surgical revascularisation and pharmacological treatment in peripheral arterial occlusive disease (PAOD) are well recognized. Therapeutic options for critical leg ischemia are consequently limited to percutaneous transluminal angioplasty (PTA) or surgical revascularisation. Unfortunately, many patients with critical leg ischemia are poor candidates for either procedure. Therapeutic angiogenesis is a novel promising tool to treat these patients. Experimental and clinical and trials of gene transfer for therapeutic angiogenesis have already shown some clinical efficacy. This review is focused on gene transfer techniques in preclinical and clinical therapeutic angiogenesis, angiogenic growth factors, vectors, delivery methods and routes. The results of clinical and experimental studies, safety and side effects of gene therapy, and the perspectives of future research are also discussed.

Animals↗
PubMed2000

Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma.

PURPOSE: Inhaled corticosteroids have beneficial effects on pulmonary function and inflammation in patients with asthma, but they also cause systemic adverse effects, such as adrenal suppression. We evaluated the therapeutic index of inhaled corticosteroids in asthmatic patients by comparing their dose-response effects on lung function, surrogate markers of airway inflammation, and tests of adrenal function. SUBJECTS AND METHODS: After a 10-day placebo run-in, we evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients, aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements were made of bronchial reactivity, exhaled nitric oxide (a marker of airway inflammation), spirometry, serum eosinophilic cationic protein concentration, and 10-hour overnight urinary cortisol excretion. Plasma cortisol levels were measured at 8 AM and after stimulation with human corticotropin releasing factor. RESULTS: For measurements of pulmonary function and exhaled nitric oxide, there was a plateau in the mean response to budesonide between 400 microg (low dose) and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg (high dose) per day. Effects on plasma cortisol levels showed maximal suppression at 1,600 microg of budesonide per day. The proportion of patients with an optimal therapeutic index, in terms of a good airway response (fourfold decrease in bronchial hyperreactivity) and minimal systemic response (overnight urinary cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose (52%) budesonide. The proportion of patients with a suboptimal therapeutic index, a good airway response with a marked systemic response (overnight urinary cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high dose. CONCLUSIONS: In patients with mild-to-moderate atopic asthma, there were dose-related effects of budesonide on surrogate markers of inflammation (bronchial hyperreactivity and serum eosinophilic cationic protein), although higher doses were associated with adrenal suppression and a decrease in the therapeutic index.

Administration, Inhalation↗
PubMed1997

Twin-to-twin transfusion syndrome: aggressive therapeutic amniocentesis.

OBJECTIVE: Untreated twin-to-twin transfusion syndrome reportedly carries nearly a 100% mortality rate. Over the last decade a number of therapeutic modalities have been attempted, including aggressive amniocentesis. This study was a retrospective evaluation of a series of 22 patients with twin-to-twin transfusion syndrome referred to our prenatal diagnostic center to determine the effectiveness in treating twin-to-twin transfusion syndrome with aggressive therapeutic amniocentesis. STUDY DESIGN: In this study three patients did not meet diagnostic criteria. For various reasons six patients did not have therapeutic amniocentesis done. One patient chose to terminate the pregnancy after three amniocenteses. Another patient chose to discontinue therapy after removal of just 100 ml of amniotic fluid. Of the 11 treated patients, the mean gestational age at diagnosis was 22 weeks 4 days (range 15 weeks 4 days to 26 weeks 4 days). RESULTS: The mean number of amniocenteses done was 5.5 (range 1 to 12). The mean total of amniotic fluid removed over the course of the pregnancy was 8.0 L (range 1100 to 24,200 ml). The mean number of days gained in these pregnancies was 56 (range 9 to 125) compared with 54 days for the untreated women. Eighty-two percent of the treated fetuses survived compared with 50% in the untreated group. Newborns in the treated group were delivered at a later gestational age and weighed more than those in the untreated group. CONCLUSIONS: Spontaneous resolution of twin-to-twin transfusion syndrome does occur. Therapeutic amniocentesis offers a simple, effective method of therapy for twin-to-twin transfusion syndrome.

Adolescent↗
PubMed1998

Digoxin visual toxicity with therapeutic blood levels of digoxin.

PURPOSE: To report two cases of digoxin-related visual disturbances associated with therapeutic blood levels of digoxin. METHODS: Case reports. One patient reported shimmering lights in the field of vision of both eyes; the second patient had a corrected visual acuity of BE, 20/40 and generalized visual field depression in both eyes. Both patients experienced these symptoms while receiving digoxin. RESULTS: Both patients had digoxin blood levels in the therapeutic range (1.7 and 1.0 ng/ml, respectively). Therapeutic levels are 0.5 to 2.0 ng/ml. After discontinuing digoxin, the first patient noted that the shimmering light symptoms resolved, and the second patient had improved visual acuity and visual fields. CONCLUSIONS: Digoxin-related visual toxicity may be associated with therapeutic blood levels of digoxin. Recognition of this entity may avoid unnecessary testing and frustration.

Aged↗
PubMed2002

[Angiogenesis and bladder cancer: trendy prognostic factor or new therapeutic target?].

Tumor-associated angiogenesis is emerging as an important prognostic factor and represents a hopeful potential therapeutic target for the cancer treatment. Bladder tumors, as all solid tumors, require an active angiogenesis to support their growth and progression. The angiogenic phenotype observed within a tumor is determined in large part by the balance between stimulatory and inhibitory inputs to the endothelial cells. Clinically, the importance of the angiogenic response observed within a tumor should be considered as an independent prognostic factor for superficial as well as invasive bladder tumors. The analysis of the angiogenic response could in the future influence the therapeutic strategy. Angiogenesis also represents a promising new therapeutic target, and is at the moment intensively tested in experimental and clinical trials. In this article, we will first review the mechanism of angiogenesis, and then its implication in bladder cancer, and as a potential therapeutic target.

Angiogenesis Inducing Agents↗
PubMed2000

Therapeutic selective nerve root block in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain: a retrospective analysis with independent clinical review.

OBJECTIVE: To investigate the outcomes resulting from the use of fluoroscopically guided therapeutic selective nerve root block (SNRB) in the nonsurgical treatment of atraumatic cervical spondylotic radicular pain. STUDY DESIGN: Retrospective study with independent clinical review. PARTICIPANTS: Twenty subjects (10 men, 10 women) with mean age 56.6 years. METHODS: Each patient met specific physical examination, radiographic, and electrodiagnostic criteria to confirm a level of cervical involvement. Those patients whose root level remained indeterminate were required to demonstrate a positive response to a fluoroscopically guided diagnostic SNRB prior to the initiation of treatment. Therapeutic injections were administered in conjunction with physical therapy. Data collection and analysis were performed by an independent clinical reviewer. MAIN OUTCOME MEASURES: Pain score, work status, medication usage, and patient satisfaction. RESULTS: Twenty patients with an average symptom duration of 5.8 months were included. An average of 2.2 therapeutic injections was administered. Follow-up data collection transpired at an average of 21.2 months following discharge from treatment. A significant reduction (p = .001) in pain score was observed at the time of follow-up. Medication usage was also significantly improved (p = .005) at the time of follow-up. An overall good or excellent result was observed in 60%. Thirty percent of patients required surgery. Younger patients were more likely (p = .0047) to report the highest patient satisfaction rating following treatment. CONCLUSIONS: This study suggests that fluoroscopically guided therapeutic SNRB is a clinically effective intervention in the treatment of atraumatic cervical spondylotic radicular pain.

Adult↗
PubMed1999

Back and hip extensor muscle function during therapeutic exercises.

BACKGROUND: Therapeutic exercises are widely used in the treatment of low back problems. Clinical knowledge about targeting the load in these exercises, however, is insufficient. This study assessed the L2 and L5 level paraspinal and gluteus maximus muscle activities in different therapeutic exercises. Intramuscular and surface electromyography (EMG) measurements were obtained to study whether surface EMG measurements can be used in the assessment of multifidus muscle function. METHODS: Eleven healthy subjects (5 men, 6 women) 21 to 38 years of age volunteered for the study. The subjects performed 18 different therapeutic exercises. During the exercises paraspinal EMG was recorded using fine wire and surface electrodes. The normalized peak and average muscle EMG activities (percentage of amplitude in maximal voluntary contraction [MVC]) during each task were determined. RESULTS: The correlations between the average intramuscular and surface activities of the normalized EMG (% of MVC) at the L2 and L5 levels were .928 and .950, respectively. The peak and average EMG amplitudes of the exercises were below 50% and 25% of MVC, respectively. At the L5 level, the multifidus peak and average EMG amplitudes (% MVC) were higher in women than in men, whereas no significant difference was found at the L2 level. In women, the normalized multifidus EMG amplitude was higher at the L5 level than at the L2 level, whereas no significant difference was found in men. In both sexes, the normalized EMG amplitude was higher in the multifidus than in the longissimus muscle. CONCLUSION: Surface EMG measurements may be used in the assessment of multifidus muscle function. Simple therapeutic exercises are effective in activating the lumbar paraspinal muscles.

Adult↗
PubMed1999

Quantitative characterization of therapeutic index: application of mixed-effects modeling to evaluate oxybutynin dose-efficacy and dose-side effect relationships.

BACKGROUND: Describing a therapeutic index for a drug is important for evaluating safe and effective dosage regimens. Therapeutic index can be evaluated as the relative position of the dose-efficacy and the dose-side effect curves. Oxybutynin XL (Ditropan XL), a once-daily oral controlled-release formulation for oxybutynin chloride, is being developed. Oxybutynin XL efficacy and side-effect data obtained from two parallel-group, randomized, controlled clinical trials were modeled to evaluate the therapeutic index. METHODS: A nonlinear mixed-effects model was used to characterize the oxybutynin dose-efficacy and dose-dry mouth relationship. Weekly urge urinary incontinence episodes, the primary efficacy variable, is a discrete variable (counts) with only non-negative integer values and was therefore modeled as a Poisson variable. The probability of dry mouth severity (the most frequently reported side effect), assessed on a categorical four-point scale, was modeled with a proportional odds model. In the modeling process, it was assumed that the time effect was the same for the active and placebo treatments and that the drug effect was additive. RESULTS AND CONCLUSIONS: The urge urinary incontinence episodes declined log-linearly, and no significant difference was observed between the two formulations. However, there was a trend toward higher efficacy with oxybutynin XL than with immediate-release oxybutynin at the same dose in one study. Dose-dry mouth analysis showed that the probability of dry mouth with an increasing dose was significantly lower with oxybutynin XL than with immediate-release oxybutynin in the second study, and a similar trend was observed in the first study. By combining the dose-urge urinary incontinence and dose-dry mouth relationship, a wider therapeutic index was predicted for oxybutynin XL than for immediate-release oxybutynin.

Adult↗
PubMed2002

Lithium chloride at a therapeutic concentration reduces Ca2+ response in protein kinase C down-regulated human astrocytoma cells.

Since the therapeutic efficacy of Li+ in the treatment of mood disorder is observed only after chronic administration, we examined whether long-term Li+ treatment with a therapeutic concentration affected the elevation of intracellular-free Ca2+ concentration ([Ca2+]i) induced by carbachol, a muscarinic receptor agonist, in 1321N1 human astrocytoma cells. Carbachol caused [Ca2+]i elevation through phosphoinositide hydrolysis in a concentration-dependent manner. Treatment of the cells with phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, for 2 min resulted in a reduction of the carbachol-induced [Ca2+]i elevation. However, PMA did not reduce the carbachol-induced [Ca2+]i elevation in cells treated with PMA for 48 h, reflecting the down-regulation of protein kinase C. Although Li+ at a therapeutic concentration (1 mM) did not affect the carbachol-induced [Ca2+]i elevation in normal cells, it potently inhibited the [Ca2+]i elevation in protein kinase C down-regulated cells. This inhibitory action of Li+ was observed in a concentration- and time-dependent manner. When protein kinase C activity was directly determined, Li+ treatment did not restore protein kinase C activity in protein kinase C down-regulated cells. [3H]Quinuclidinyl benzylate, a muscarinic receptor ligand, bound to membranes derived from normal and protein kinase C down-regulated cells with a similar Kd and Bmax, and Li+ did not affect these parameters of [3H]quinuclidinyl benzylate binding. These results indicated that Li+ at a therapeutic concentration reduced the muscarinic receptor-mediated increased in [Ca2+]i under the protein kinase C-deficient condition without affecting muscarinic receptor or protein kinase C activity.

Astrocytoma↗
PubMed1996

Outpatient therapeutic ERCP: a series of 262 consecutive cases.

BACKGROUND: Because of possible complications, it has been common practice to admit most if not all patients undergoing therapeutic ERCP. Therefore, little descriptive data exist on the safety of outpatient therapeutic ERCP. METHODS: We assessed 262 consecutive ERCPs in 209 patients undergoing outpatient therapeutic ERCP over a 5-year period, with particular attention to the development of complications. All outpatient endoscopic sphincterotomies and stent placements performed over a 5-year period were prospectively entered into an ongoing data base that was used for the analysis. In addition, hospital and office records for all patients were retrospectively reviewed, including a 30 to 45 day follow-up in a private office setting. RESULTS: Suspected or documented choledocholithiasis was the most common indication for ERCP and was present in 132 (50%), followed by malignant obstruction in 77 (29%), type I sphincter of Oddi dysfunction (on the basis of symptoms, liver test abnormalities, and bile duct dilatation) in 36 (14%), chronic pancreatitis in 10 (3.8%), HIV cholangiopathy in 4 (1.5%), and other conditions in 3 (1.1%). Overall, 181 patients (69%) underwent a sphincterotomy. The 30-day post-ERCP complication rate was 5.7% (95% CI: 3.2% to 9.3%), occurring in 15 of 262 cases. Complications necessitating hospitalization developed in 9 of the 262 ERCPs for a rate of 3.4% (95% CI: 1.6% to 6.4%). The mean duration of hospital stay among patients admitted for a complication was 2.7 +/- 1.8 days (range, 1 to 7 days). All patients were discharged without permanent sequelae. No 30-day procedure-related fatalities were reported. CONCLUSION: In this selected series of 262 consecutive cases, endoscopic sphincterotomy and stent placement were safely performed in an ambulatory setting. Prior to recommending a generalized change in existing practice, however, this finding requires validation with larger series of cases, including the performance of other outpatient therapeutic ERCP techniques.

Adolescent↗
PubMed1981

Iron deficiency in one-year-old infants: comparison of results of a therapeutic trial in infants with anemia or low-normal hemoglobin values.

The purpose of this study was to determine the Hgb response to a therapeutic trial of iron in infants with anemia compared to those with low-normal hemoglobin values. Hgb was determined in 1.128 one-year-old infants. The 278 infants (25%) who had an Hgb less than 11.5 gm/dl were given a three-month oral course of ferrous sulfate (3 mg iron/kg/day); the regimen was satisfactorily completed by 188 infants. Of the 75 infants whose initial capillary Hgb was in the anemic range (Hgb less than 11.0 gm/dl), 45% had an increase in venous Hgb greater than or equal to 1.0 gm/dl. Of the 113 infants with initial capillary values in the low-normal range (11.0 to 11.4 gm/dl), 28% had greater than or equal to 1.0 gm/dl Hgb response. Despite the lower rate of response in the low-normal group, almost half of the infants with a greater than or equal to 1 gm/dl response would have been missed by using the generally accepted cutoff value of 11 gm/dl for a therapeutic trial. Because of the low cost and simplicity of a therapeutic trial, we favor including the low-normal Hgb group for a therapeutic trial of iron in order to avoid missing iron-responsive individuals among groups of infants with a similarly high prevalence of iron deficiency anemia.

Adult↗
PubMed1998

The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents.

Neuronal nicotinic acetylcholine receptors (NAChRs) are pentameric ligand-gated ion channel receptors which exist as different functional subunit combinations which apparently subserve different physiological functions as indicated by molecular biological and pharmacological techniques. It is possible to design and synthesize novel compounds that have greater selective affinities and efficacies than nicotine for different NAChRs, which should translate into different behavioral profiles and therapeutic potentials. Examples of NAChR agonists studied are nicotine, SIB-1508Y, SIB-1553A and epibatidine. These compounds have different degrees of selectivity for human recombinant NAChRs, different neurotransmitter release profiles in vitro and in vivo and differential behavioral profiles. Preclinical studies suggest that SIB-1508Y is a candidate for the treatment of the motor and cognitive deficits of Parkinson's disease, whereas SIB-1553A appears to have potential as a candidate for the treatment of Alzheimer's disease. Epibatidine has a strong analgesic profile, however the ratio between pharmacological activity and undesirable effects is so low that it is difficult to envisage the use of this compound therapeutically. Nicotine has a broad profile of pharmacological activity, for instance demonstrating activity in models for cognition and analgesia. As for epibatidine, the adverse effects of nicotine severely limits its therapeutic use in humans. The discovery of subtype-selective NAChR agonists such as SIB-1508Y and SIB-1553A provides a new class of neuropsychopharmacological agents with better therapeutic ratios than nonspecific agents such as nicotine.

Animals↗
PubMed1998

Therapeutic amniocentesis using a vacuum bottle aspiration system.

BACKGROUND: Therapeutic amniocentesis has been performed traditionally by gravitational drainage or syringe aspiration. We describe a technique for relatively rapid, large-volume therapeutic amniocentesis using a negative-pressure vacuum bottle aspiration system. TECHNIQUE: The procedure involves insertion of a 20-gauge spinal needle into the amniotic cavity followed by connection to a 1-L vacuum bottle via noncollapsible tubing. EXPERIENCE: During a 5-year period, 86 therapeutic amniocenteses were performed on 26 women. The amniotic fluid removal rate was 89 mL/minute. There were three instances of transient preterm labor, three cases of ruptured membranes within a week of the procedure, and no cases of abruption, chorioamnionitis, or fetal distress. CONCLUSION: The vacuum bottle aspiration technique for therapeutic amniocentesis permits expeditious removal of large volumes of amniotic fluid safely and effectively.

Amniocentesis↗
PubMed1994

Therapeutic drug monitoring in the pediatric intensive care unit.

Drugs are administered in the pediatric intensive care unit using either a target-effect or a target-concentration strategy. In the former, drug dose is escalated until the predetermined target-effect is achieved, no further pharmacologic effect is obtained with incremental increases in dose, or toxicity supervenes. When the target-concentration strategy is used, drug therapy is adjusted to achieve serum/plasma drug concentrations within an accepted therapeutic range. This strategy does not recognize interindividual differences in drug responsiveness. Therapeutic drug monitoring in the pediatric intensive care unit is further confounded by the limited data available concerning the effects of the other technologies used on drug disposition and the paucity of information related to therapeutic agents in pediatric patients. Clearly therapeutic drug monitoring in the pediatric intensive care unit is a daunting challenge.

Adolescent↗