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Biomedical subjects

K Allegaert

Publications and source records attributed to K Allegaert.

At least 19 recordsLinked to original sources
PubMed2006

Impact of ibuprofen administration on renal drug clearance in the first weeks of life.

The administration of ibuprofen or any other nonselective cyclooxygenase (COX) inhibitor drug in early neonatal life is associated with a reduction of glomerular filtration, which reduces the elimination of drugs dependent on renal function for clearance. However, the relationship between COX inhibitor drug indication (prophylactic or therapeutic) and the magnitude of this effect remains unclear. Observations collected in two population pharmacokinetic studies, in preterm neonates, investigating amikacin and vancomycin were used to estimate: i) the impact of ibuprofen administration on the clearance of these drugs; and ii) the difference between prophylactic and therapeutic administration of ibuprofen on this clearance. Prophylactic administration of ibuprofen to preterm neonates on the first day of life to enhance closure of an asymptomatic patent ductus arteriosus (PDA) reduced amikacin clearance by 21% while coadministration of ibuprofen to induce closure of a symptomatic PDA resulted in an 18% reduction in vancomycin clearance in the first month of postnatal life. A significant and clinically relevant reduction in drug clearance is observed when ibuprofen is coadministered independent of indication, postmenstrual or postnatal age. Population modeling with covariate analyses can provide us with the tools to further disentangle the impact of nonselective COX-inhibitors on renal drug clearance.

Age Factors↗
PubMed2006

Maturational changes in the in vivo activity of CYP3A4 in the first months of life.

OBJECTIVE: To document maturational changes of the in vivo activity of CYP3A4 in the first months of life. METHODS: The contribution of tramadol (M), O-demethyl tramadol (M1, CYP2D6-mediated) and N-demethyl tramadol (M2, CYP3A4-mediated) to the overall elimination of tramadol and the log M/M2 was assessed in 24-hour urine collections during continuous intravenous tramadol administration. Correlations with perinatal characteristics (postnatal age (PNA) and postmenstrual age (PMA)) were studied. RESULTS: Of the total amount of tramadol administered in a 24-hour interval to 25 neonates and young infants (PMA 25 - 53 weeks), 34.5% (SD 6.1) were retrieved in the urine as parent compound or metabolite in a 24-hour interval. This retrieved material consisted primarily of tramadol 79% (SD 18), M1 10% (SD 17) and M2 3% (SD 3.4). The contribution of M (r2 = -0.53), M1 (r2 = 0.46) and M2 (r2 = 0.16) to overall M elimination correlated with increasing PMA. The mean log M/M2 was 1.44 (SD 0.46) and there was an inverse correlation between the log M/M2 ratio and PMA (r2 = -0.43, 95% CI for r = -0.84 to -0.34, p = 0.0006) and PNA (r2 = -0.25, 95% CI for r = -0.78 to -0.16, p = 0.008). The maturational half-life of the log M/M2 ratio was 16 - 20 weeks. In a multiple regression model, PMA was the only significant variable accounting for the interindividual variability in log M/M2. CONCLUSIONS: PMA was found to be the most important maturational change determing the in vivo activity of CYP3A4. The activity of CYP3A4 is relatively delayed in the first months of life compared to the developmental changes in CYP2D6 activity described earlier, however, the overall weak correlations reflect that PMA explains only in part the interindividual variability observed.

Age Factors↗
PubMed2006

Cryotherapy versus laser photocoagulation for threshold retinopathy of prematurity: impact on early postoperative clinical recovery.

In a retrospective study in preterms treated with either cryotherapy (n= 16, 2000-2001) or laser photocoagulation (n= 19, 2002-2005) for threshold retinopathy, a significant decrease in duration of postoperative ventilation, in postoperative administration of analgesics and in time until regain of full enteral feeding was documented in infants who received laser photocoagulation. We therefore conclude that - compared to cryotherapy - laser treatment for threshold retinopathy is associated with a faster clinical postoperative recovery.

Cryotherapy↗
PubMed2005

Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity.

BACKGROUND: Tramadol is potentially a very useful pain relief medication in neonates and infants. It is primarily metabolized into O-demethyl tramadol (M1) by CYP2D6. Data concerning tramadol disposition and CYP2D6 activity in young infants are not available. METHODS: A population pharmacokinetic analysis of tramadol and M1 time-concentration profiles was undertaken using non-linear mixed-effects models (NONMEM), based on newly collected data on tramadol and M1 time-concentration profiles in neonates and young infants (n=20) and published studies on intravenous tramadol in children and adults. M1 formation served as a surrogate for CYP2D6 activity. RESULTS: Tramadol clearance was described using a two-compartment linear model with zero-order input and first-order elimination. Clearance increased from 25 weeks post-conception age (PCA) (5.52 litre h(-1) [70 kg](-1)) to reach 84% of the mature value by 44 weeks PCA (standardized to a 70 kg adult using allometric '1/4 power' models). The central volume of distribution decreased from 25 weeks PCA (256 litre [70 kg](-1)) to reach 120% of its mature value by 87 weeks PCA. Formation clearance to M1 contributed 43% of tramadol clearance, but had no relationship with PCA. There was a weak non-linear relationship between PCA and M1 metabolite clearance. CONCLUSIONS: Maturational clearance of tramadol is almost complete by 44 weeks PCA. A target concentration of 300 microg litre(-1) is achieved after a bolus of tramadol hydrochloride 1 mg kg(-1) and can be maintained by infusion of tramadol hydrochloride 0.09 mg kg(-1) h(-1) at 25 weeks PCA, 0.14 mg kg(-1) h(-1) at 30 weeks PCA, 0.17 mg kg(-1) h(-1) at 35 weeks PCA, 0.18 mg kg(-1) h(-1) at 40 weeks, 0.19 mg kg(-1) h(-1) at 50 weeks PCA to 1 yr, 0.18 mg kg(-1) h(-1) at 3 yr and 0.12 mg kg(-1) h(-1) in adulthood. CYP2D6 activity was observed as early as 25 weeks PCA, but the impact of CYP2D6 polymorphism on the variability in pharmacokinetics, metabolism and pharmacodynamics of tramadol remains to be established.

Adult↗
PubMed2005

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate.

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood-brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.

Analgesics, Opioid↗
PubMed2005

Ibuprofen and cerebral oxygenation and circulation.

The effect of prophylactic administration of ibuprofen on the cerebral circulation in preterm babies was measured with near infrared spectroscopy. No significant difference in the change in cerebral blood volume, change in cerebral blood flow, or tissue oxygenation index was found between administration of ibuprofen or placebo.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Clinical pharmacology of non opioid analgesics in neonates.

An integrated approach of neonatal analgesia starts with the systematic evaluation of pain and should be followed by effective interventions, mainly based on the appropriate (i.e. safe and effective) administration of analgesics. In contrast to the more potent opioids, data on the pharmacokinetics and -dynamics of non-opioid analgesics in this specific population are still rare or even lacking. We therefore evaluated various aspects of developmental pharmacology of non-opioid analgesics (paracetamol, ibuprofen, acetylsalicyl acid) in neonates. We first performed a single dose propacetamol study in preterm and term neonates. Based on these preliminary findings, a repeated dose administration scheme was developed and tested and maturational aspects from preterm till teenage were documented. Although non-selective COX-inhibitors might be effective in the treatment of postoperative or inflammatory pain syndromes in neonates, potential efficacy should be balanced against the drugs' safety profile. Neonatal renal clearance strongly depends on glomerular filtration rate (GFR) and GFR itself strongly depends on the vaso-dilatative of prostaglandins on the afferent arterioli. We therefore evaluated the impact of the administration of ibuprofen or acetylsalicylic acid on renal clearance in preterm infants and hereby used amikacin clearance as a surrogate marker. We hereby documented the negative effect of ibuprofen on glomerular filtration rate in preterm infants up to 34 weeks and we were able to show that ibuprofen and acetylsalicylic acid had an equal impact on the glomerular filtration rate.

Acetaminophen↗
PubMed2004

Effects of co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin in preterm infants during the first days of life.

The aim of this study was to assess the effects of intravenous co-administration of ibuprofen-lysine on the pharmacokinetics of amikacin during the first days of life in preterm infants. The pharmacokinetics of amikacin were retrospectively calculated in a cohort of 73 neonates (gestational age <31 weeks) who received either ibuprofen-lysine or placebo following inclusion in the multicentre ibuprofen prophylaxis study. Assuming a one-compartment model with instantaneous input and first-order output, there was no significant difference in the median distribution volume (0.63 vs. 0.59 liters/kg), but the median serum half-life (16.4 vs. 12.4 h) of amikacin was significantly longer (p <0.02), and the clearance (0.36 vs. 0.6 ml/kg/min; p <0.005) of amikacin was significantly lower in infants who received ibuprofen-lysine. We conclude that the time interval between consecutive amikacin administrations should be prolonged, if ibuprofen-lysine is co-administered.

Amikacin↗
PubMed2004

Continuous infusion of medications in very low birth weight infants.

OBJECTIVE: To develop a safe and accurate method for the administration in the neonatal intensive care unit of several potent medications as a continuous infusion without overloading the infant, especially the very low birth weight (VLBW) infant by diluents. METHOD: The method designed is based on a weight-adapted solution limiting the diluent administration and allowing for a versatile modulation of dose administration. As this method was initially designed for VLBW infants, the point of departure of this method is a standard maximal fluid load of 0.3 ml/h for each medication, delivered in a low compliant circuit with a high-precision syringe driver. Solutions are made for 24 h, which is a compromise between drug stability and repeated pressure drops in the circuit when changing the syringe and administration set. To translate a prescription into a solution a conversion factor is calculated. In addition to the calculation principle, this conversion factor is given for a number of commonly used drugs in neonatal care. CONCLUSIONS: In our experience, the method described adds to the safety and accuracy of continuous drug administration in neonatal care.

Humans↗
PubMed2004

Methemoglobinemia and hemolysis after enteral administration of methylene blue in a preterm infant: relevance for pediatric surgeons.

A preterm infant had methaemoglobulinemia and hemolytic anemia after enteral administration of methylene blue. The dye was administered to exclude a tracheoesophageal fistula. Methylene blue is a noxious product, especially in neonates. It should be considered a potential cause of acquired methemoglobulinemia, even after enteral administration.

Esophagus↗
PubMed2004

The use of methohexital during chest tube removal in neonates.

BACKGROUND: The aim of the study was the evaluation of the effect of methohexital during chest tube removal (CTR) in neonates. METHODS: Evaluation was based on the degree of sedation (grades 1-4) and relaxation (grades 1-4) and trends in vital signs heart rate, mean arterial blood pressure (MAP), oxygen saturation at time points (-10, -5, -3, -1, 0, 1, 3, 5, and 10 min) before and after administration of methohexital. A multidimensional pain scale [Leuven Neonatal Pain Scale (LNPS)] was used to evaluate pain expression. Effective sedation and relaxation (grade >2) would enable the physician to perform CTR without difficulties. Paired Wilcoxon was used to compare vital signs and pain expression before and after the procedure. RESULTS: Twenty-two procedures in 22 infants were recorded. Eleven infants were ventilated and 21 infants were having intravenous analgesics during CTR. Birth weight was 2645 g (range 1235-4500 g). Postnatal age was 6 days (range 1-80 days). Methohexital had no effect on ventilatory weaning, MAP or oxygen saturation. Heart rate increased from 144 (49) to 162 (43) (P = 0.012) b.min(-1). Sedation and relaxation were effective (>grade 2) and lasted for <5 min. No major side effects were documented. Adequate analgesia by LNPS was more difficult to evaluate as clinical pain evaluation was not feasible during full muscular relaxation. CONCLUSIONS: Administration of methohexital for CTR resulted in adequate sedation and relaxation without major side effects in neonates. This approach should be compared with other strategies.

Analgesics↗
PubMed2004

Threshold retinopathy at threshold of viability: the EpiBel study.

AIM: To describe incidence, co-morbidity characteristics, and risk factors associated with threshold retinopathy of prematurity (ROP) in survivors with a gestational age (GA) of < or =26 weeks at birth. METHODS: Retrospective analysis of perinatal data of all inborn survivors in all perinatal centres of Belgium in the period 1999-2000 (EpiBel cohort) believed to be between 22 and 26 weeks GA at time of delivery. Data on survivors who did and survivors who did not develop threshold ROP were compared (chi(2), Mann-Whitney U) and logistic regression was performed. RESULTS: Of 303 admitted infants 175 (58%) were discharged alive. Incidence of major retinopathy (> or =stage 3) and of threshold ROP was 25.5% and 19.8% in survivors. Associated central nervous abnormalities were documented in six (17%) and associated chronic lung disease in 19 (54%) threshold ROP infants. Threshold ROP without additional morbidity characteristics at discharge was documented in 14 (40%) infants. Besides often reported risk factors, renal insufficiency (creatinaemia>1.5 mg/dl) was a risk factor to develop threshold ROP (p<0.0015) (chi(2)). Days of respiratory support (OR 1.02; 95% CI 1.002 to 1.039), number of transfusions (OR 1.118; 95% CI 1.030 to 1.214), and renal insufficiency (OR 3.31; 95% CI 1.344 to 8.196) remained independent risk factors to develop threshold ROP in this cohort in a stepwise logistic regression model (MedCalc). CONCLUSIONS: Incidence of threshold ROP is high at the limits of viability. Renal insufficiency is a risk factor to develop threshold ROP in this cohort.

Belgium↗