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Biomedical subjects

K Hoppu

Publications and source records attributed to K Hoppu.

17 recordsLinked to original sources
PubMed1992

Inositol supplementation in premature infants with respiratory distress syndrome.

BACKGROUND: Inositol influences cellular function and organ maturation. Feeding premature infants inositol-rich breast milk increases their serum inositol concentrations. Whether inositol supplementation benefits infants receiving fluids for parenteral nutrition, which are inositol-free, is not known. METHODS: We carried out a placebo-controlled, randomized, double-blind trial to determine the effects of administering inositol (80 mg per kilogram of body weight per day) during the first five days of life to 221 infants with respiratory distress syndrome who were receiving parenteral nutrition (gestational age, 24 to 32 weeks; birth weight, less than 2000 g). All the infants were treated with mechanical ventilation and some with surfactant as well. The primary end point was survival at 28 days without bronchopulmonary dysplasia. RESULTS: The 114 patients given inositol had significantly lower mean requirements for inspiratory oxygen (P less than 0.01) and mean airway pressure (P less than 0.05) from the 12th through the 144th hour of life than did the 107 infants given placebo. Eighty-one infants given inositol and 51 given placebo survived without bronchopulmonary dysplasia (71 vs. 55 percent; P = 0.005). In the 65 infants given surfactant, however, inositol had no effect on the degree of respiratory failure. Thirteen infants given inositol and 21 given placebo had retinopathy of prematurity (13 vs. 26 percent; P = 0.022); none of the infants given inositol had stage 4 disease, whereas 7 of those given placebo did (0 vs. 9 percent; P = 0.012). Among the infants given placebo, those who had poor outcomes (death, bronchopulmonary dysplasia, or stage 4 retinopathy of prematurity) had lower serum inositol concentrations during days 2 through 7 than those who had good outcomes (P less than 0.01). CONCLUSIONS: The administration of inositol to premature infants with respiratory distress syndrome who are receiving parenteral nutrition during the first week of life is associated with increased survival without bronchopulmonary dysplasia and with a decreased incidence of retinopathy of prematurity.

Bronchopulmonary Dysplasia↗
PubMed1991

Accidental astemizole overdose in young children.

6 cases of accidental astemizole poisoning in children have been reported to the Finnish Poison Information Center. The children were aged 1 year 7 months to 3 years 4 months and had taken doses of 2.5 to 16.7 mg/kg, at least twelve times that recommended. In 2 children the overdose was verified by measurement of drug concentrations. Despite measures to prevent drug absorption prolonged QTc-interval, a sign of cardiac toxicity, was found in all 5 children on whom an electrocardiogram was available for analysis, and severe ventricular arrhythmias developed in 1. Young children with accidental astemizole overdose should be carefully monitored in hospital. Similar precautions may be justified in cases of overdose with other selective H1-histamine receptor antagonists.

Accidents, Home↗
PubMed1991

Pharmacokinetically determined cyclosporine dosage in young children.

To account for the individual variability in cyclosporine pharmacokinetics and the non-existence of dosing recommendations in young children, we studied the pharmacokinetics of cyclosporine before renal transplantation in ten children aged 1.1-2.5 years, to determine the appropriate individual dose. Our aim was to reach a steady-state cyclosporine blood level of 200-300 micrograms/l, 8 h after a dose in the first days after renal transplantation. Cyclosporine was given as a single oral dose (10 mg/kg) or as a 4-h i.v. infusion (3 mg/kg), and the blood concentration was determined for 24 h by a specific monoclonal radioimmunoassay. The mean terminal cyclosporine half-life (t1/2) was 9.3 h (range 2.8-20.4), blood clearance 10.8 ml/min per kilogram (range 6.8-22.7) and volume of distribution 2.8 l/kg (range 1.4-4.7). The bioavailability of oral cyclosporine was low; the mean amount absorbed was 21.8% of the administered dose (range 11-35). The mean calculated dose needed to attain the intended predose blood cyclosporine level of 200-300 micrograms/l at steady-state was 5 mg/kg per day for i.v. and 21 mg/kg per day for oral administration. In view of the short t1/2, we used three doses/day. The validity of the predicted doses is shown by the mean cyclosporine doses used during the first 10 days after transplantation, which were 93.5% of the calculated oral and 96.6% of the calculated i.v. doses. The observed mean cyclosporine concentration during the same period was 196 micrograms/l.

Cyclosporins↗
PubMed1991

Evidence for pre-hepatic metabolism of oral cyclosporine in children.

1. The pharmacokinetics of cyclosporine were investigated before renal transplantation in 20 children aged 1.1 to 16.8 years. Cyclosporine was given as a single oral dose (10 mg kg-1) or as a 4 h i.v. infusion (3 mg kg-1). 2. The blood drug concentration was measured by both specific and nonspecific monoclonal radioimmunoassays. 3. The mean oral availability of cyclosporine was 20.6% (range 10.8-34.1%). 4. The mean ratio of AUCs measured by nonspecific and specific r.i.a. was 1.96 (range 1.4-2.7) after oral administration and 1.43 (range 1.1-2.0) after i.v. administration. The mean difference between the ratios was 38.5% (P = 0.0001). The ratio of AUCnonspecific to AUCspecific was inversely related to blood drug clearance (r = 0.57; P = 0.009). 5. The findings are suggestive of presystemic, pre-hepatic metabolism of cyclosporine which could contribute to the low, and highly variable bioavailability of this drug.

Administration, Oral↗
PubMed1989

Surfactant proteins in the diagnosis of fetal lung maturity. II. The 35 kd protein and phospholipids in complicated pregnancy.

The major surfactant protein with a molecular weight of 35 kd and also saturated phosphatidylcholine and phosphatidylglycerol were analyzed in specimens of amniotic fluid; 68 were from cases of maternal diabetes, 41 from preeclampsia or maternal hypertension, 26 from premature rupture of the fetal membranes, and 45 from normal pregnancies. The relationship between the individual surfactant components was studied after covariance adjustment for the length of gestation. In severe early-onset preeclampsia, the 35 kd surfactant protein/saturated phosphatidylcholine ratio was significantly higher than in the other pregnancies. In diabetic pregnancies (classes B to D without preeclampsia), the phosphatidylglycerol/saturated phosphatidylcholine ratio was lower than in the other pregnancies. Isolated surfactant complex showed similar abnormalities. In severe early-onset preeclampsia and insulin-dependent diabetes without vascular disease, the phosphatidylglycerol/saturated phosphatidylcholine ratio correlated negatively with fetal growth. In four samples of amniotic fluids from cases of severe early-onset preeclampsia, the 35 kd protein falsely predicted lung maturity. All had abnormally high 35 kd protein/saturated phosphatidylcholine ratios (greater than 2 SD of controls). According to the present results, the 35 kd protein may give a false mature test result in severe preeclampsia.

Amniotic Fluid↗
PubMed1989

Changes in trimethoprim pharmacokinetics after the newborn period.

The pharmacokinetics of trimethoprim administered orally or intravenously were investigated in six infants aged 1.7 months to 1.1 years. In these infants trimethoprim had a mean half life of 4.6 hours; this was comparable with the values found in young and school age children (3.8 and 5.4 hours respectively) and about a quarter of the half life in newborns. The volume of distribution (1.5 l/kg) was smaller than in newborns but larger than in young or school age children (0.9 and 1.1 l/kg respectively). The plasma clearance in these infants (3-3 ml/min/kg) was slightly larger than in newborns or in either group of older children (2.9 and 2.4 ml/min/kg respectively). Thus the most dramatic changes in trimethoprim pharmacokinetics seem to occur during the first two months of life. A reduced daily dose of trimethoprim is necessary during the first two months only. An increased daily dose, by addition of a third dose each day, is recommended from two months.

Age Factors↗
PubMed1988

Trimethoprim in the treatment of acute urinary tract infections in children.

In the first study to assess the effect of trimethoprim in the treatment of acute urinary tract infections in children, we compared it with sulphisoxazole. Eighteen girls, mean age 5.3 years, were treated with trimethoprim 6 mg/kg/day. Seventeen girls, mean age 5.0 years, treated with sulphisoxazole 150-200 mg/kg/day for 10 days served as controls. All infections were cured. Three patients in each group had reinfections during the 6 months of follow-up. In each group, one of the reinfections occurred within 2 weeks after the end of the treatment. One patient developed a rash from sulphisoxazole and so required drug change. No other adverse effects were observed. We conclude that trimethoprim is as effective as sulphisoxazole in the treatment of simple acute urinary tract infections of children and recommend it, in the dosage used, as an alternative first-choice drug, especially for patients who have had side effects from sulphonamides or nitrofurantoin.

Acute Disease↗
PubMed1987

Determination of trimethoprim in pediatric samples by high-performance liquid chromatography.

We describe and evaluate modifications to a known high-performance liquid chromatography assay of trimethoprim. The sensitivity, specificity and wide range of linearity (0.11-690 mumol/l) of this method make it suitable for analysing samples with large variations in volume and concentration. We have used it to study the pharmacokinetics of trimethoprim in children, including newborns. Automated injection is a useful option if the sample volume is not limited. The recovery (at 3.44 mumol/l) of the method was 99.8% with a coefficient of variation of 6.8% for manually injected samples. The corresponding results for automated injection were 97.9% and 12.8%.

Blood Specimen Collection↗
PubMed1987

Food and guar decrease absorption of trimethoprim.

Absorption of trimethoprim suspension 3 mg/kg has been studied in 12 healthy adult volunteers when given alone, with food or with food and guar, using a randomised Latin-squares study design. Serum and urine trimethoprim concentrations were followed for 24 h. The mean peak serum concentration was higher when fasting subjects were treated (mean: 2.35, 1.84 and 1.97 micrograms/ml for the fasting, food and food + guar groups, respectively; ANOVA p less than 0.001 for the difference between fasting and non-fasting values). The times of the peak serum concentrations did not differ. Food ingestion decreased the area under the curve by 22.2%, as did food + guar. For maximal efficacy trimethoprim should be administered between meals.

Absorption↗
PubMed1987

Inositol supplementation in respiratory distress syndrome: relationship between serum concentration, renal excretion, and lung effluent phospholipids.

Inositol or placebo was given to 48 small preterm infants with respiratory distress syndrome (mean birth weight 1365 g, gestational age 30.1 weeks) between 48 hours and 10 days of age. The dose of inositol, 40 mg/kg every 6 hours, was at least as high as amounts received in full preterm human milk feedings. Serum inositol concentration increased between days 2 and 3 from a mean of 566 mumol/L to 823 mumol/L in the infants given supplement and fell from 451 mumol/L to 292 mumol/L in the controls. On day 16, serum inositol values remained higher in the infants given supplement than in those given placebo (mean 334 mumol/L vs 146 mumol/L, P = 0.014). The infants who developed bronchopulmonary dysplasia had significantly higher renal inositol clearance, lower inositol intake, and lower serum inositol concentrations. Inositol supplementation increased the saturated phosphatidylcholine/sphingomyelin ratio in tracheal aspirates. According to these results, supplementation with inositol in preterm infants leads to a rise in serum inositol concentration and improvement in the surfactant phospholipids. Inositol deserves further study as a dietary supplement for immature preterm infants who do not receive full human milk feeds.

Double-Blind Method↗
PubMed1987

Trimethoprim pharmacokinetics in children with renal insufficiency.

We studied the pharmacokinetics of trimethoprim in 14 children (two neonates) with renal insufficiency. They were 1 week to 16.4 years old and had glomerular filtration rates (GFR) between 10.8 to 72.3 ml/min/1.73 m2. The half-life (t1/2) of trimethoprim was inversely related to the GFR. The relation followed a power curve (correlation of t1/2 with GFR: r = -0.86; P less than 0.001). The slower elimination rate was mainly the result of lowered renal clearance of trimethoprim. The volume of distribution (Varea) was, in most patients, in the upper normal range for children. In some of the patients, chiefly infants with severe renal insufficiency, the Varea was larger than normal. In some individuals the pharmacokinetics of trimethoprim deviated from that to be expected from the GRF. We recommend reduced daily doses of trimethoprim if the GFR is less than 30 ml/min/1.73 m2. The reduction should be proportional to the reduction in GFR and primarily take the form of a prolonged dose interval.

Absorption↗
PubMed1987

Age differences in trimethoprim pharmacokinetics: need for revised dosing in children?

The pharmacokinetics of trimethoprim was studied in children (nine girls 1.05 to 3.57 years old and nine girls 7.55 to 9.70 years old) with urinary tract infections and 12 healthy adults (27.07 to 44.62 years old) to investigate any age-related changes. Serum and urine concentrations were measured during 24 hours. The groups did not differ in the time or the height of the peak serum concentration. Thereafter the children had lower serum concentrations. They had a shorter elimination half-life (means: 1 to 3 years, 3.7 hours; 8 to 10 years, 5.4 hours; adults, 11.2 hours), because of the smaller volume of distribution (0.86 l/kg; 1.08 l/kg; 1.31 l/kg) and higher total clearance (2.8 ml/min/kg; 2.4 ml/min/kg; 1.4 ml/min/kg). The higher clearance in children was mainly nonrenal (metabolism). Calculation of the pharmacokinetic variables per unit of body surface area modified the age differences considerably. Compared with present dosage recommendations, trimethoprim in larger daily doses per kilogram of body weight for the children is suggested. The daily dose should be increased primarily by shortening the dose interval.

Adult↗