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Biomedical subjects

M O Richard

Publications and source records attributed to M O Richard.

At least 37 records · Page 2Linked to original sources
PubMed1989

Pharmacokinetics of propofol in young children after a single dose.

The pharmacokinetics of propofol were studied following a single bolus injection (2.5 mg kg-1) in 10 healthy children (4-7 yr). Propofol was distributed rapidly and extensively (Vss 10.9 (1.2) litre kg-1) and cleared rapidly from the body (Cl 30.6 (2.9) ml min-1 kg-1). With the exception of a larger central compartment volume (V alpha 722 (113) ml kg-1), these data are similar to those reported for young adults who received an identical dose and who underwent sampling over the same period. The larger value of V alpha is consistent with the higher induction dose requirement reported for children.

Child↗
PubMed1989

Maturation of AFMU excretion in infants.

The maturation of the N-acetyltransferase-dependent AFMU production from caffeine was studied during infancy. The group of children (N = 14) consisted of 4 premature newborn infants and ten 1-19 month-old infants who received caffeine citrate solution for the treatment and prevention of apnea. Caffeine, AFMU, 1X and 9 other metabolites were measured in urine using HPLC. The AFMU/1X ratio did not vary significantly in this population with increasing age. In one of the infants serially studied, the AFMU/1X ratio increased dramatically between 6 and 12 months of age. This observation suggests that the maturation of N-acetyltransferase activity is not completed before 1 year of age implying that acetylator status cannot reliably be determined before that age. Patients studied before 1 year of age whose AFMU/1X ratio was below 0.4 may be either true slow acetylators or still immature fast acetylators.

Acetylation↗
PubMed1989

Pharmacokinetic interactions between theophylline and rioprostil.

The study is of double-blind crossover design. The effects of rioprostil, an analogue of prostaglandin E1, at a dose of 300 micrograms b.d., and placebo on the kinetic of slow-release theophylline are investigated. Eight healthy male volunteers participate in the study, each study period lasting for one week. During the first period, the doses of theophylline are altered in response to measured theophylline levels, 200 mg or 400 mg b.d. Regardless of placebo or rioprostil treatment, side effects appear before day 6 and are related specifically to theophylline administration. Blood samples are taken on days 4 and 5 to check steady-state plasma levels of theophylline and on days 6 and 7 to determine the main pharmacokinetic parameters. The same schedule is used for the second period of treatment. The achievement of steady-state concentration is verified. The mean pharmacokinetic parameters do not show a significant difference when slow-release theophylline is given alone or with rioprostil. These results are likely to be clinically relevant and, therefore, the theophylline dose should not be changed if rioprostil is prescribed at the same time as the theophylline.

Adult↗
PubMed1988

Maturation of caffeine metabolic pathways in infancy.

The maturation of the different pathways of caffeine metabolism was studied during infancy. The group of children (n = 14) consisted of four premature newborn infants and 10 older infants who received caffeine citrate solution. Caffeine and 11 of its metabolites were measured by HPLC. Total demethylation and N3- and N7-demethylation increase exponentially with postnatal age; the plateau is reached by 120 days and accounts for 58.6%, 90.5%, and 79.3%, respectively. N1-demethylation shows no variation with postnatal age. It is suggested that N3-demethylation is more important in young infants than in adults and that maturation of N1-demethylation occurs later than 19 months of age. 8-Hydroxylation is mature as early as 1 month of age and may be higher in infants than in adults. Acetylation is not mature before at least 1 year of age. Differences in maturation rate of acetylation may be related in part to genetic acetylator status.

Acetylation↗
PubMed1988

Gentamicin monitoring in neonates.

The elimination of gentamicin (G) was studied in 103 neonates (30 premature) during the first month of life after 2.5 mg/kg i.v. (as infusion) over 20-30 min. G plasma levels, measured by EMIT assay, were obtained before and at 1, 2, 3, and 6 h after infusion. We derived individual first-order kinetic parameters and designed optimal dose regimens. G plasma clearance, half-life, and recommended dose (mg/kg/h) changed exponentially with postnatal age during the first 14 days of life. No significant changes in kinetic values were noted during the first 3 days of life; however, they varied linearly with gestational age when they were measured during this period. Apgar score at 10 min and blood urea nitrogen significantly influenced the same parameters. The predictive value of a designed dose regimen was evaluated at steady-state, after dosage adjustment using two plasma concentration values: the minimum plasma concentration was below 2 mg/L in 93% of the patients; the plasma concentration observed within 1 h after completion of the infusion was (mean +/- SD) 5.33 +/- 0.97 mg/L. Our data suggest that 2.5 mg/kg every 12 h is appropriate in most neonates except for 0-2-day-old premature infants who require 2.5 mg/kg every 18 h. Monitoring of G plasma levels is advisable in infants with low Apgar score and/or renal failure.

Age Factors↗
PubMed1988

Developmental changes of caffeine elimination in infancy.

Five neonates (4 premature) and 16 infants (6 prematurely born), 15-588 days old, received caffeine as citrate salt for apnea. Plasma samples were collected 0, 2, 4, 6 h after a dose and before the next scheduled one. Patients 8 and 9 were serially studied. Caffeine plasma concentrations were determined using HPLC. The caffeine elimination half-life and clearance varied linearly with gestational age and exponentially with postnatal age, the plateau being reached during the second trimester of life. Dose regimen guidelines as a function of postnatal age were derived from individually calculated doses and dosing intervals in order to achieve, at steady state, a caffeine mean plasma concentration of 11 mg/l with a minimum of 7.5 mg/l and a maximum of 14.5 mg/l. We suggest dosing intervals for infants before 1 month, 1-2 months, 2-4 months and after 4 months to be equal to 24, 12, 8 and 6 h, respectively. The individual recommended dose varies from 2 to 10 mg/kg (as caffeine base) making caffeine monitoring mandatory in infants.

Aging↗
PubMed1988

Maturation of caffeine N-demethylation in infancy: a study using the 13CO2 breath test.

Four premature neonates and eight infants 1-19 months old received caffeine for apnea. The usual morning oral dose was substituted by 1,3,7 13C-trimethylxanthine (13C-tri CAF) as the citrate salt. Five breath samples were collected the day before (day 1) and the day of 13C-tri CAF administration (day 2). Plasma (after each breath collection) and urine were collected on day 2. 13C-CO2 exhalation was determined by isotope ratio mass spectrometry. Caffeine and its metabolites were measured using high-pressure liquid chromatography. Assessment of the labeled CO2 in the breath revealed no detectable 13C-tri CAF N-demethylation activity in infants before 45 wk postconceptional age. However, demethylation (as urinary metabolites) has been detected before that age. Two-, 4-, and 6-h cumulative excretion of 13C-tri CAF as 13C-CO2 increased with postnatal age and correlated with caffeine plasma clearance (r = 0.840, p less than 0.01). These results were consistent with those obtained for urinary metabolites. In one infant (19 months old) the cumulative excretion of 13C-CO2 while crying was 65% of the value observed during quiet breathing. The measurement of caffeine demethylation using the caffeine CO2 breath test is feasible in infants and is a safe and noninvasive method to determine age related changes in P4501-dependent N-demethylase activity.

Apnea↗
PubMed1987

Effect of natural progesterone treatment during pregnancy on fetal testosterone and sexual behavior of the male offspring in the mouse.

The effect of maternal exposure to progesterone upon the fetal pituitary-gonadal axis and the sexual behavior of the male offspring of mice were studied. Daily injection of progesterone from days 14 to 16 of pregnancy reduced testosterone production in the fetus but caused a significant increase in circulating LH levels. Progesterone-exposed males showed no alteration in anogenital distance or in body weight at any time from birth to adulthood. At 80-90 days of age males from control and progesterone-exposed groups did not differ from each other in testis and seminal vesicle weights. However, in the latter group, there was a marked reduction in the percentage of males that displayed mount, intromission and ejaculation patterns. These findings indicate that in utero exposure to pharmacological doses of progesterone that do not cause abnormalities of male internal and external genitalia may interfere with masculine behavior in adulthood. This alteration could partially be due to diminished peripheral testosterone levels during the prenatal period.

Animals↗
PubMed1986

Effect of propranolol on alpha-amino-isobutyric acid and water kinetics in the materno-fetal unit of the rat.

Pregnant Sherman rats were given propranolol (a) per os (50 mg X kg-1, twice a day) on days 17-19 of gestation, (b) by constant rate infusion: osmotic minipumps (6 mg X kg-1 X day-1) from day 13 of gestation. On day 20 (a-treated) or 21 (b-treated), [14C]-AIB + [3H]-H2O were injected intravenously; plasma and tissue samples were collected at different times up to 4 h (a-treated) or at 2 h (b-treated) for radioactivity measurements. Whatever the treatment, no difference was found between control and treated animals for all parameters studied (number of fetuses; weight, protein; DNA; [14C]-AIB or [3H]-H2O tissue levels) except in propranolol-treated mothers where maternal heart [14C]-AIB uptake was decreased and where fetal plasma and tissue [3H]-H2O levels where higher than control at 5 min. Another set of experiments were performed in a-treated rats. On day 20, each mother was anesthetized with ether and injected as above; maternal plasma sample and one feto-placental unit were collected at different times within 15 min after injection. For this period, [14C]-AIB uptake and mainly [3H]-H2O diffusion were increased in placentae and fetuses of propranolol-treated dams. Arterial blood pressure did not change throughout the experiment in propranolol-treated animals, but decreased in controls. Heart rate was slowed down in the former compared to controls. Thus, in our experimental conditions, propranolol treatment: does not modify fetal weight; has no effect on AIB placental transfer and tissue uptake, and could protect towards the stress of anesthesia and surgical injuries, since H2O transfer was impaired in control but not in treated animals.

Aminoisobutyric Acids↗
PubMed1986

Buflomedil kinetics in patients with liver disease.

The pharmacokinetics of single intravenous (100 mg) and oral (450 mg) doses of buflomedil was studied in 3 and 6 patients respectively, suffering from chronic liver disease. Comparisons of buflomedil kinetic parameters between the patients and healthy subjects indicate a significant increase in AUC0 infinity, T beta, u' and a significant decrease in Cle', Clnr when the patients received the oral dose, but no significant differences when the patients received the intravenous dose probably due to the small number of patients explored. The elimination of buflomedil is impaired in chronic hepatic disease. It seems advisable to reduce the usual dose to half its value when the prothrombin index is around 50% associated with a low albumin concentration and a low factor V.

Administration, Oral↗
PubMed1984

Effect of maternal progesterone exposure on fetal testosterone in mice.

The effect of maternal exposure to progesterone on plasma testosterone levels was studied in fetal mice. A daily subcutaneous injection of 2 mg progesterone to mice from day 14 to 17 of pregnancy resulted in a significant decline of circulating testosterone levels in male fetuses (p less than 0.05). A single injection of progesterone to mothers on day 18 of pregnancy leads to the same effect in male fetuses but increased significantly plasma testosterone levels in female ones (p less than 0.01). The testes of fetuses from progesterone-exposed mothers produced in vitro less testosterone than those of controls (p less than 0.01). These results show that both long- and short-term maternal exposure to pharmacological concentrations of progesterone reduce testosterone production in the male fetus. The nature of this mechanism is yet unknown, but it is suggested that the change of plasma testosterone levels may result from a local inhibition of the fetal testicular function.

Animals↗
PubMed1984

Pharmacokinetics of buflomedil after intravenous administration in patients with chronic renal failure.

The pharmacokinetics of single intravenous doses of buflomedil were studied in nine patients with chronic renal failure. The mean buflomedil half-life was 5.38 h (range 1.78-11.8 h); the mean buflomedil total clearance was 11.8 l/h (range 2.67-37.2 l/h). Comparisons of buflomedil kinetic parameters between the uraemic patients and healthy subjects revealed significant decreases in the renal elimination percentage u, the renal clearance Clr; significant increase in elimination half-life from the central compartment and no significant differences in the other parameters. Chronic renal failure is associated with a significant alteration in buflomedil elimination. This study suggests to reduce the usual dosage to half its value in the renal disease.

Adult↗
PubMed1983

Pharmacological interaction between nitroglycerin and aspirin after acute and chronic aspirin treatment of healthy subjects.

The interaction between nitroglycerin (NTG) and aspirin was investigated in 7 healthy subjects in order to test whether aspirin could block the haemodynamic response to NTG; the doses used were NTG 0.8 mg, and aspirin 0.5 g for chronic and 1 g for acute treatment. The plasma levels of NTG and various physiological parameters (heart rate, diastolic arterial pressure, end diastolic diameter, and end systolic diameter) were measured during the 30 minutes after the administration of NTG. An increase in NTG Cmax and AUC was observed after both aspirin treatment. The changes in physiological parameters produced by NTG were enhanced by the two treatments, although the differences were not statistically significant. The results indicate complex pharmacokinetic and pharmacodynamic interactions between NTG and aspirin.

Adult↗
PubMed1983

[Risk indices of reagin allergy. I. The rhesus phenotype and specific IgE production].

The authors have studied the frequency of the rhesus phenotype elements CC, Cc or cc, in relationship with the different specific IgE antibodies determined by Radio immunoassay (Phadebas IgE Rast). They found a regular distribution of these phenotype elements, whatever the different IgE among all subjects with family respiratory allergic diseases. On the other hand, among all subjects who have no family atopic history, rhesus cc phenotype is significantly more frequent. This situation is observed in both sexes equally. To understand, the causal mechanicism, serum IgA and IgM were compared. A good correlation was found only with CC rhesus allergic patients. It is suggested that these patients are carrying a non yet identified immune response gene, whereas cc rhesus subjects could be suffering from an important transmucosal penetration of the environmental antigens.

Adolescent↗