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Biomedical subjects

M J Boutroy

Publications and source records attributed to M J Boutroy.

At least 37 records · Page 2Linked to original sources
PubMed1990

Placental transfer and perinatal pharmacokinetics of betaxolol.

Betaxolol levels in blood were monitored in the perinatal period in 28 pregnant hypertensive women and in their babies. In the mothers betaxolol concentrations at delivery ranged from less than 1 to 115 ng.ml-1 after doses of 10 to 40 mg.day-1. The apparent blood half-life was 15.6 to 22.1 h mean (19 h). Umbilical cord levels indicated a rapid equilibrium between fetal and maternal units (ratio 0.93) within few hours after dosing. Milk betaxolol concentrations, measured in few cases, exceeded those in blood by a factor of 3. Amniotic fluid concentrations were similar to those observed in maternal venous blood and umbilical cord blood. In neonates, the blood betaxolol half-life ranged from 14.8 to 38.5 h, with a definite trend towards a negative correlation with gestational age. A 11-61% rise in the betaxolol concentration was observed in 64% of the neonates during the first 12 h of extrauterine life. The data indicate that betaxolol kinetics is not altered in pregnant women and they stress the need for careful and prolonged (72-96 h) intensive monitoring of neonates born to hypertensive mothers treated with beta-blocking agents.

Adult↗
PubMed1989

Pharmacokinetics of antihypertensive drugs in the neonatal period.

A consistent body of evidence indicates that in the preterm and full-term newborn drug disposition is reduced when compared to that of infants, grown-up children, and adults. Newborns are rarely treated directly with antihypertensive agents; however they can be exposed to the action of various antihypertensive drugs in utero and during their first week of extrauterine life in the case of hypertensive mothers treated through pregnancy. In such cases, the persistence of the antihypertensive agent during the first days of life may have important consequences on neonatal haemodynamics and on the function and the maturation of vital organs such as lungs and kidneys. The available information on the placental transfer and neonatal pharmacokinetics of alpha-methyldopa, clonidine, acebutolol, atenolol, betaxolol, metoprolol, propanolol, oxprenolol, and latetalol, are reviewed. Each product has its own pharmacokinetic characteristics which should influence, depending on the clinical situation, the therapeutic choice. In the presence of comparable efficacy, preference should be given to compounds with high bioavailability, eliminated mainly via metabolic degradation, with no active metabolites. In all cases, treatment should be discontinued 8-12 h before delivery.

Antihypertensive Agents↗
PubMed1989

Fetal effects of maternally administered clonidine and angiotensin-converting enzyme inhibitors.

Clonidine is an alpha-adrenergic agonist. It crosses the placenta extensively. No teratogenic effect is known in animals or in clinical practice but the question of a possible long-term behavioral teratogenicity has recently been pointed out. Clonidine does not seem to be deleterious for fetal growth, mortality and morbidity. Nothing is known about the consequences on fetal hemodynamics. The angiotensin-converting enzyme inhibitors (ACE inhibitors) captopril and enalapril act by inhibiting the formation of angiotensin II from angiotensin I. They cross the placenta. No teratogenic effect has been proved for either drug. A high rate of fetal mortality has been reported in several animal species for captopril but the available clinical data are not sufficient to assess the role of the ACE inhibitors in perinatal mortality, intrauterine growth retardation, and fetal distress in humans. The fetal hemodynamic parameters may be affected by captopril administration to the mother: blood pressure falls, plasma renin activity increases, ACE activity decreases. As for most antihypertensive drugs, available information on the consequences of clonidine and ACE inhibitors in the neonate and the infant now seem sufficient to appreciate the risk in maternal therapy. In contrast, they are still insufficient considering their known effects on fetal hemodynamics, cardiovascular adaptation, and brain tolerance, with or without hypoxia, as well as for their possible long-term adverse effects.

Adult↗
PubMed1989

[Open trial of betaxolol in the treatment of arterial hypertension in pregnancy, pilot study].

The efficacy and the safety of betaxolol (BTX), a cardio-selective adrenoceptor blocking agent with a long half life, was tested in 22 hypertensive pregnant women. BTX doses varied from 10 to 40 mg/day. BTX given as monotherapy (n = 19) or associated to dihydralazine (n = 3) led to a satisfactory control of arterial blood pressure (ABP). In the mother, the drug was very well tolerated. (table; see text) The fetal safety, evaluated by mean of cardiotocography and echography was also satisfactory. Fetal heart rythm was significantly slowed following first intake of BTX and remained stable until delivery; there was only one case of intra-uterine growth retardation pre-existing to the pharmacological treatment. Nine deliveries were ceasarian [fetal distress (n = 1); poor control ABPI (n = 1); obstetrical reasons (n = 7)]. Seventeen neonates were full-term and six were premature (twins included). The state of neonates at birth was very satisfactory (Apgar at 5 minutes greater than 9 in 21/23). Glycemia less than 1.66 mmoles/1 in two neonates, was normal within 24 to 48 hours. In conclusion, BTX was very efficacious in controlling increased blood pressure in pregnant women and its safety in the mother, the fetus and the newborn was very good.

Adolescent↗
PubMed1987

Fetal and neonatal effects of the beta-adrenoceptor blocking agents.

The placental transfer of beta-adrenoceptor blocking agents has been well established in the last years. Randomized and/or controlled studies have given a less pessimistic view of the consequences of these drugs on the fetal and neonatal adaptation. In fact, the beta-blockers are able to produce hypotension, bradycardia, respiratory troubles in the newborn infant, troubles which are generally slight when the neonates are full-term. However, even if in good clinical conditions, this kind of neonate should be carefully monitored for at least the first 2 days of life.

Adrenergic beta-Antagonists↗
PubMed1986

Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures.

Eighteen newborns (gestational age 28 to 42 weeks and post-natal age 0.5 to 44 days) suffering from convulsions not controlled by phenobarbital were treated with clonazepam 0.1 mg/kg (8 cases) or 0.2 mg/kg (10 cases) administered by slow intravenous infusion. The plasma half-lives in these "phenobarbital pretreated neonates' were of the same order of magnitude as those reported in adults (20-43 h). Post-natal age did affect clearance, which was 50-70% less than in adults and older children. At the end of the infusion period, plasma clonazepam ranged from 28 to 117 ng/ml in the 0.1 mg/kg group and from 99 to 380 ng/ml in the 0.2 mg/kg group. In the former an immediate therapeutic response was observed in 7 out of 8 cases, and in the latter a significant and somehow delayed effect on convulsion was present only in 6 cases. The data suggest that optimal therapeutic response might already have been achieved with the 0.1 mg/kg dose. Higher doses and toxic concentrations of clonazepam may be detrimental to complete control of seizures and may expose the newborn to an unnecessary risk of adverse events.

Adult↗
PubMed1986

To nurse when receiving acebutolol: is it dangerous for the neonate?

The concentrations of acebutolol and of its main active metabolite diacetolol in milk and plasma were studied in 7 hypertensive mothers treated with acebutolol, a cardioselective beta-adrenoceptor blocking agent. Clinical monitoring on their newborn babies was also done, as well as measurement of plasma level of the drug in them. The ratio between milk and plasma concentrations ranged from 1.9 to 9.2 for acebutolol and from 2.3 to 24.7 for diacetolol, and in any given milk sample, the diacetolol concentration was always higher than that of acebutolol. In a newborn infant, plasma concentrations of the two transplacentally acquired substances was raised when breast feeding started and remained high. Clinical signs of pharmacological beta-blockade were observed. Evaluation of the iatrogenic risk shows that pharmacologically active amounts of acebutolol might be received by a neonate if the daily maternal dosage exceeds 400 mg/day and/or renal function in the mother is impaired.

Acebutolol↗
PubMed1986

Plasma kinetics of parenteral tocopherol in premature infants.

The potential use of alpha-tocopherol (alpha-T) in the prevention of retrolental fibroplasia led to a study of the plasma kinetics of alpha-T. A dose of 20 mg alpha-tocopherol acetate (alpha-T-Ac) was injected subcutaneously in 5 premature newborns. alpha-T-Ac and alpha-T were assayed by high-pressure liquid chromatography. The maximum plasma concentration of alpha-T-Ac was 2.0 +/- 0.60 mg/dl (mean +/- SEM). alpha-T concentrations remained above 0.5 mg/dl from 8 to 168 h with a mean peak plasma concentration of 2.15 +/- 0.45 mg/dl. alpha-T-Ac absorption and elimination half-lives were 7.0 +/- 0.7 and 23.2 +/- 9.0 h, respectively; alpha-T appearance and elimination half-lives were 12.8 +/- 3.1 and 80.6 +/- 21.0 h. The proposed dosage to keep a plasma level higher than 0.5 mg/dl is 20 mg of alpha-T-Ac every 5 days.

Absorption↗
PubMed1980

Pharmacokinetics of indomethacin in the premature infant.

Indomethacin (I) pharmacokinetics was evaluated in 6 premature infants who received the drug for treatment of patent ductus arteriosus. Administered by oral or rectal route, I (0.2 mg/kg/24 h X 3) was promptly absorbed with peak plasma concentrations attained within 1 and 3 h. The elimination of I appeared to follow two compartment open model kinetics, with terminal plasma half-lives ranging from 30 to 90 h. Apparent plasma clearance values were between 0.076 and 0.335 ml/min/kg. Ductal closure was observed in 4 of the 6 infants. Data point to a possible relationship between therapeutic effects and I plasma concentrations.

Creatinine↗
PubMedDate not supplied

Rat neonates renal function after beta-receptors and adrenoceptors blockade during pregnancy.

Pregnant Wistar rats were given by subcutaneous route 1 of 3 different adrenoreceptor blockers, 2 of them mainly beta-blockers. P5 and P7 group received propranolol (5 and 7 mg/kg respectively), L10 and L20 groups received labetalol (10 and 20 mg/kg) and B5 group received betaxolol (5 mg/kg). Drugs were given daily from the 7th to the 16th day of gestation. A control group received saline injections. 16 out 24 treated mothers delivered prematurely on the 21st day of gestation. Functional renal parameters were studied in neonates on the first day of life. Renal function of the full term rats prenatally exposed were compared with controls. Average body weight was higher in P5 but lower in L10-L20-B5 groups. Diuresis increased in L20. Creatinine clearance, urinary/plasmatic creatinine ratio and urea clearance decreased in L10-L20 groups and fractional excretion of H2O increased in L20. Thus these adreno- and beta-blockers given to pregnant rats induced a shorter gestation. Moderate functional renal effects were observed in all neonates.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[The choice between theophylline and caffeine in the treatment of apnea in premature infants].

In a double blind study, two comparable groups (each n = 10) of premature infants less than 34 weeks of gestational age, with idiopathic apnea were given an IV treatment of either theophylline or caffeine. The loading doses were respectively 6 and 10 mg/kg and the maintenance doses were 2 and 1.25 mg/kg every 12 hours. In both groups, apneas greater than or equal to 15 s. with or without bradycardia were similarly reduced (p less than 0.01). Both drugs increased significantly the respiratory rate. Compared to caffeine, theophylline induced a significant acceleration of heart rates, an increase in urinary sodium excretion, more frequent gastrointestinal intolerance and behavioral changes. Plasma concentrations of theophylline were less stable than those of caffeine. These data suggest that a single daily dose of caffeine should be preferentially used in the treatment of idiopathic apneas of prematurity.

Caffeine↗