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  • 1
    Electronic Resource
    Electronic Resource
    Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 647-649 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00543504
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  • 2
    Electronic Resource
    Electronic Resource
    Acetaminophen accumulation in pediatric patients after repeated therapeutic doses (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 57-59 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF02395207
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  • 3
    Electronic Resource
    Electronic Resource
    Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 637-642 
    Details
    ISSN: 1432-1041
    Keywords: vancomycin ; pharmacokinetics ; dosage guidelines ; infants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to characterize the pharmacokinetics of vancomycin and to develop optimal dosage guidelines in infants. Thirteen infants between the ages of 13 to 183 days were enrolled. All had been born prematurely, and average gestational age, postconceptional age, and actual body weight were 29.8 weeks, 38.2 weeks, and 2.1 kg respectively. Multiple blood samples were obtained from each patient after 72 h of therapy. Serum inhibitory and bactericidal titres were determined for peak and trough samples. There were good correlations between total body clearance of vancomycin and both postconceptional age (r=0.86) and actual body weight (r=0.87). This information was used to develop vancomycin dosage guidelines in premature infants. The regression line for vancomycin daily dosage requirements vs postconceptional age may be useful for determining initial dosage recommendations. There were also good correlations between vancomycin serum concentrations and serum inhibitory and cidal titres. Peak and trough concentrations in the therapeutic range (peak, 25–35 µg/ml; trough, 5–10 µg/ml) corresponded to titres of ≥ 1:8 and 1:2 to 1:8 respectively. Based on these data we suggest the following dosage guidelines for vancomycin: 10 mg/kg 12 hourly for 30–34 weeks postconceptional age and 〈1.2 kg actual body weight; 10 mg/kg 8 hourly for 30–42 weeks postconceptional age and 〉1.2 kg actual body weight; 10 mg/kg 6 hourly for 〉42 weeks postconceptional age and 〉2.0 kg actual body weight. Thus, doses which are lower than currently recommended are needed for infants born prematurely. Furthermore, the initial dose of vancomycin can easily be determined using an infant's postconceptional age.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00637600
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of ibuprofen in febrile children (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 427-428 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00265858
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of dexamethasone in premature neonates (1996)
    Springer
    European journal of clinical pharmacology 49 (1996), S. 477-483 
    Details
    ISSN: 1432-1041
    Keywords: 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
    URL: http://dx.doi.org/10.1007/BF00195934
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  • 6
    Electronic Resource
    Electronic Resource
    The relation between type of renal disease and renal drug clearance in children (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 195-197 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00315480
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus infection (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 291-293 
    Details
    ISSN: 1432-1041
    Keywords: Fluconazole ; absorption ; pharmacokinetics ; HIV infection ; children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The objective of this study was to determine the pharmacokinetics of fluconazole after oral administration in children with human immunodeficiency virus (HIV) infection. After an overnight fast, a single dose of either 2 mg·kg−1 or 8 mg·kg−1 was administered in a suspension; five children received 2 mg·kg−1 and four 8 mg·kg−1 (ages 5–13 years). Blood samples were collected at various times on day 1, and once daily on days 2–7 after the dose. Fluconazole serum concentrations were measured by gas chromatography. At the dose of 2 mg·kg−1, the Cmax, AUC (0–∞), and t1/2 ranged from 2.3–4.4 μg·ml−1, 84.9–136 μg·h·ml−1, and 19.8–34.8 h, respectively. At the dose of 8 mg·kg−1 the Cmax, AUC (0–∞), and t1/2 ranged from 5.4–12.1 μg·ml−1, 330–684 μgh·ml−1, and 25.6–42.3 h, respectively. When compared with published data in healthy adults, fluconazole achieved similar serum concentrations in the present group of children, indicating a nearly complete degree of absorption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00198314
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 281-284 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00545228
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of netilmicin in premature infants (1986)
    Springer
    European journal of clinical pharmacology 29 (1986), S. 635-637 
    Details
    ISSN: 1432-1041
    Keywords: netilmicin ; prematurity ; infants ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of netilmicin were studied in 12 premature infants with proven or presumed sepsis during the first month of life. Eleven of 12 patients received netilmicin 2.5 mg/kg intravenously every 12 h while one 770-gram birth weight infant received 2.5 mg/kg every 18 h. Mean steady-state peak and trough concentrations were 8.9 µg/ml and 2.8 µg/ml, respectively. Of twelve patients, 11 had trough serum concentration above 2 µg/ml and four had trough serum concentrations above 3 µg/ml. Mean total body clearance of netilmicin was 0.84 ml/min/kg. The mean clearance of 0.72 ml/min/kg was substantially lower in patients with a mean postnatal age of 2.7 days than the clearance of 1.10 ml/min/kg in patients with a mean postnatal age of 23 days. The mean apparent volume of distribution was 0.63 l/kg; and the mean elimination half-life was 8.6 h. A three-fold interpatient variation in pharmacokinetic parameters was seen. These data suggest the need for careful monitoring of netilmicin serum concentration in premature infants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635907
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 515-517 
    Details
    ISSN: 1432-1041
    Keywords: rifampicin ; cerebrospinal fluid ; children shunt infections ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg · kg−1, administered intravenously 1 h prior to surgery. The peak serum concentrations ranged from 13.5–26.7 μg · ml−1; cerebrospinal fluid concentrations ranged from 0.12–3.0 (mean: 1.4) μg · ml−1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.291 · kg−1 · h−1, 1.11 · kg−1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100-to 1000-fold against Staphylococcus epidermidis. However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02336694
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