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  • 1
    ISSN: 1432-198X
    Keywords: Key words Amlodipine ; Hypertension ; Ambulatory blood pressure ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07±0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%–50% every 5–7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29±0.11 mg/kg per day for those 〈13 years, 0.16±0.11 mg/kg per day for those ≥13 years, 0.23±0.14 mg/kg per day for essential, hypertension and 0.24±0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 40 (1991), S. 593-597 
    ISSN: 1432-1041
    Keywords: Dopamine ; Newborns ; critically ill patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5–20 μg · kg−1 · min−1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013–0.3 μg/ml. Total body clearance averaged 115 ml · kg−1 · min−1. The apparent volume of distribution and elimination half life averaged 1.8 1 · kg−1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 49 (1996), S. 477-483 
    ISSN: 1432-1041
    Keywords: Key words Dexamethasone ; Premature neonates; pharmacokinetics ; bronchopulmonary dysplasia ; infant: newborn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objective: Dexamethasone is frequently used in premature neonates with bronchopulmonary dysplasia, however little is known about its disposition in this population. Methods: We evaluated the pharmacokinetics of dexamethasone in 9 premature neonates with a mean gestational age of 27.3 weeks and a postnatal age of 21.8 days. Results: There was a strong relationship between clearance (4.96 ml⋅min−1⋅kg−1) and gestational age (r = 0.884). Pharmacokinetic parameters were grouped based on a gestational age of less than 27 weeks (Group I) and greater than 27 weeks (Group II). Mean clearance in group I and group II was 1.69 and 7.57 ml ⋅min−1⋅kg−1, respectively. Mean distribution volume in group I and II was 1.26 and 2.19 l⋅kg−1, respectively. No significant relationships were noted between the disposition of dexamethasone and ventilator requirements or adverse effects. Conclusion: The pharmacokinetics of dexamethasone in premature neonates was related to gestational age.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 195-197 
    ISSN: 1432-1041
    Keywords: Cefotaxime ; Renal insufficiency ; desacetylcefotaxime ; pharmacokinetics ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It is generally assumed that the renal clearance of drugs in patients with renal impairment are affected to a similar extent regardless of the type of renal disease (intact nephron hypothesis). We have studied the effect of underlying renal disease on the pharmacokinetics of cefotaxime and desacetylcefotaxime in two groups of children (ages 7 to 16 y) with varying degrees of renal dysfunction. Patients in group 1 (n=5) had intrinsic renal disease and those in group 2 (n=5) had extrinsic renal disease, as identified by the primary renal lesion. After a single intravenous dose of cefotaxime timed blood and urine samples were collected for 24 h; cefotaxime and desacetylcefotaxime were measured by HPLC. There were no significant differences between the groups in age, body surface area, urine output, creatinine clearance, total body clearance, nonrenal clearance, renal clearance, and volume of distribution at steady state of cefotaxime, and renal clearance of desacetylcefotaxime. However, the renal clearance: creatinine clearance (CLR:CLCR) ratios for both cefotaxime [1.34 in group 1 vs. 0.51 in group 2] and desacetylcefotaxime [1.58 in group 1 vs. 0.75 in group 2] were statistically significant between the two groups. Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR=24 ml·min−1·1.73 m−2). In contrast, patients in group 2 (CLCR=49) ml·min−1·1.73 m−2) had an average CLR:CLCR ratio less than 1 for both cefotaxime and desacetylcefotaxime, suggesting that renal tubular transport mechanisms did not remain functional in these patients. Our findings suggest that the effect of renal insufficiency on the renal elimination of cefotaxime and its metabolite desacetylcefotaxime may depend on the cause of renal insufficiency.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: Meperidine ; Midazolam ; Sedation ; endoscopy ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract We conducted a randomized, double-blind trial evaluating the efficacy and safety of meperidine 2 mg·kg− (M) and meperidine 2 mg·kg− plus midazolam 0.05 mg·kg− (M+M) in 40 pediatric outpatients (age 1 to 17 years) undergoing upper endoscopy procedures. The physician and nurse performing the procedure were asked to rate cooperation, emotional status, drowsiness, and overall efficacy. A blinded observer recorded the frequency of negative behaviors indicating distress, vital signs, and oxygen saturation before, during, and after the procedure. No significant differences were noted in the overall efficacy of the regimens. Good or excellent efficacy was noted in 15 of 21 children (71%) in the M group and 15 of 19 children (79%) in the M+M group by physicians; nurses assigned a good or excellent rating for 14 of 21 (67%) and 13 of 19 (68%) in the M and M+M groups, respectively. Immediately following the procedure, amnesia was noted in 4 of 17 (23%) patients who received M versus 14 of 18 (78%) patients who received M+M (P=0.002). Of the children who received M+M, the amnesia tended to occur more frequently in older children (〉11 years, 8 children, rate of amnesia 100%) than in younger children (≤11 years, 6 of 10 evaluable children, rate of amnesia 60%). There was no significant difference between the frequency of negative behaviors, rate of adverse effects, or changes in vital signs or oxygen saturation noted with the two drug regimens. We conclude that although the two sedation regimens produced similar efficacy, the combination of M+M may be preferred over M alone to enhance amnesia. Additional trials of M+M for sedation prior to other procedures are needed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 40 (1991), S. 427-428 
    ISSN: 1432-1041
    Keywords: Ibuprofen ; children ; fever ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients. We studied 17 patients (age 3–10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media. Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients). Multiple blood samples were collected over 8 hours and analyzed by HPLC. The maximum observed serum concentrations of ibuprofen ranged from 17–42 μm·ml−1 at 5 mg·kg−1 and 25–53 μm·ml−1 at 10 mg·kg−1 doses. Pharmacokinetics did not appear to be affected by ibuprofen dose. Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml·min−1·kg−1, and 1.6 h, respectively in patients at 5 mg·kg−1 doses; the corresponding values were 1.2 h, 1.4 ml·min−1·kg−1, and 1.6 h in those receiving 10 mg·kg−1 doses. There was no relationship between age and ibuprofen kinetics. No adverse effects occurred in any patients. These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 281-284 
    ISSN: 1432-1041
    Keywords: methenamine ; bacteriuria ; urinary acidifier ; formaldehyde ; ascorbic acid ; drug efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one l/day.Proteus vulgaris, Pseudomonas aeruginosa, andE. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 647-649 
    ISSN: 1432-1041
    Keywords: tobramycin ; newborn infants ; intrapatient variations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p〉0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p〉0.05), and elimination half-life averaged 8.6 and 7.1 h (p〉0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants ⩽1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p〈0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p〈0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants ⩽1.5 kg birth weight.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    ISSN: 1432-1041
    Keywords: acetaminophen ; pediatric patients ; fever therapy ; accumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)−1 after the first dose and 0.202 (ml/min/kg)−1 at steady-state (p〈0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 30 (1986), S. 719-722 
    ISSN: 1432-1041
    Keywords: rimantadine ; influenza A ; adverse effects ; serum concentration ; infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Rimantadine has been shown to be more active in vitro and less toxic than amantadine in adults with influenza A disease. Because of a lack of studies in pediatric patients, we designed a study to evaluate serum concentrations and adverse effects of rimantadine in infants receiving repeated doses. Fourteen hospitalized infants (ages 1–10 months) were given rimantadine syrup at 3 mg/kg/dose in single daily doses during influenza season. Blood samples were obtained prior to dose and at various intervals up to 8 h after doses on the fifth to ninth days of therapy. Adverse effects were assessed based on clinical status, activity level, hematologic and biochemical parameters during 10-day therapy. Steady-state rimantadine peak serum concentration ranged from 100 to 574 ng/ml and time to achieve peak concentration ranged from 2.5 to 6.0 h after the doses. No adverse effects were seen except hematuria in one infant; this patient had the highest rimantadine concentration and longest treatment duration. Hematuria resolved during a follow-up evaluation on the ninth day after stopping therapy. Our data suggest that 1. rimantadine can be given safely at repeated doses of 3 mg/kg/dose in a convenient once-daily regimen; 2. the steady-state peak serum concentrations and time to achieve peak concentration may vary substantially in infants receiving same oral doses; and 3. possible association of adverse effects and high serum concentration or long treatment duration of rimantadine needs further evaluation in small infants.
    Type of Medium: Electronic Resource
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