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Biomedical subjects

M O Richard

Publications and source records attributed to M O Richard.

At least 55 records · Page 3Linked to original sources
PubMed1982

[3H]-Salbutamol placental transfer in pregnant rats on the 19th day of gestation.

[3H]-salbutamol added in tracer doses (approximately equal to 250 nmol per animal) to the carrier solution (20 mg/kg) was injected intraperitoneally to pregnant rats on the 19th day of gestation. Some experiments were performed with intravenous administration (approximately equal to 2.5 microCi in 300 microliters 9 g/l NaCl). Drug distribution was studied in the maternal and fetal plasma, lung and liver, and in the placenta and amniotic fluid. 10% of the maternal salbutamol plasma radioactivity was recovered in the fetal plasma, in accordance with earlier findings reported from our laboratory using human placental lobules in vitro.

Albuterol↗
PubMed1982

Maternofetal transfer of two benzodiazepines. Effect of plasma protein binding and placental uptake.

The influence of plasma protein binding on the maternofetal transfer of diazepam was studied in the perfused human placental lobule. Substitution of buffered salt perfusate in both maternal and fetal circuits for a perfusate with plasma proteins did not alter diazepam transfer significantly. Diazepam placental uptake was shown to be important in perfusion, with both types of perfusates. Comparison with the less liposoluble and less protein-bound benzodiazepine, fosazepam, revealed a marked difference in placental uptake but not in maternofetal transfer. In incubation studies, the kinetics of placental uptake confirmed this difference.

Blood Proteins↗
PubMed1982

Pharmacokinetics of tiapride and absolute bioavailability of three extravascular forms.

The pharmacokinetic properties of a single 200-mg dose of tiapride were studied in eight healthy volunteers (four males and four females). The drug was administered by i. v., i. m., and p. o. routes (solution and tablets). Plasma and urine concentrations were determined by a high-performance liquid chromatography. The results were compatible with a linear two-compartment model. The half-life in the disposition phase ranged from 2.19 h to 4.55 h (mean 3.23 h). Peak plasma concentrations were always reached within 2 h. The percentage of absorption of the i. m. and the two p. o. formulations varied from 49.3 to 98.9%. The renal clearance varied from 11.8 to 24.9 l/h. The drug was mainly eliminated in unmetabolized form in the urine (75.6%).

Absorption↗
PubMed1981

Transfer of Salbutamol in the human placenta in vitro.

The maternal-fetal transfer of Salbutamol was studied in vitro, in dual perfusion of isolated human placental lobules. The fraction of drug transferred to the fetal side was compared to reference substances:((14)C)-antipyrine and ((3H)-inulin. Salbutamol transfer (12%) represents about 39% of antipyrine and five times of inulin transfer. Studies with varying Salbutamol concentrations in the maternal arterial perfusate revealed that the drug transfer to the fetal side was effected by a flow-dependent diffusion process. We conclude that the reported effects on the fetus following a maternal drug infusion are mediated by the drug transferred across the placenta.

Albuterol↗
PubMed1981

Lung catecholamines and cyclic nucleotides during perinatal development in the rat. Possible relationships with biochemical and morphological differentiation.

In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5'-monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes.

Animals↗
PubMed1980

Pharmacokinetics of buflomedil after intravenous and oral administration.

Pharmacokinetics studies were conducted in 4 patients who received buflomedil 100 mg intravenously and in 3 volunteers who received buflomedil 450 mg per os. Buflomedil concentrations were determined by a gas liquid chromatography method. Buflomedil levels declined multiphasically with a mean clearance after intravenous administration of -0,034 (1 h-1 kg-1). The decline appeared to be monophasic after oral administration. In both cases the overall half-life is short, mean 2.07 hrs (range, 1,47-2,6 hrs).

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of hydroxy-3(S)-dihydroquinidine in healthy volunteers after intravenous and oral administration.

The pharmacokinetics of hydroxy-3(S)-dihydroquinidine (HDHQ) were studied in 6 healthy volunteers following a 15 min intravenous infusion of a 300 or 400 mg dose, a 300 mg oral dose in solution and a 300 mg tablet administration on three separate occasions (random order) with at least one week intervals. Using a specific HPLC assay for HDHQ, the post-infusion and post-absorption plasma HDHQ concentrations declined bi-exponentially. Both oral forms of HDHQ were absorbed rapidly (tmax 1 h-1.2 h) with an absolute bioavailability of the oral solution (F = 0.54 to 0.93) which was not significantly different from that of the tablet (F = 0.66 to 0.90). HDHQ was rapidly and extensively distributed to the tissues with a high steady-state volume of distribution (6.82 +/- 1.85 l X kg-1). Mean elimination half-life was 6.7 +/- 1.4 h after IV infusion, 8.4 +/- 1.7 h after the oral solution and 11.3 +/- 4.4 h after the tablet administration. HDHQ was partially eliminated from the body in the unchanged non-conjugated form by the urine and renal clearance represented approximately 50% of the total body clearance. These results show that HDHQ is rapidly and almost completely absorbed and has potential for a twice daily administration regimen for the treatment of cardiac arrhythmias.

Administration, Oral↗
PubMedDate not supplied

Amiodarone pharmacokinetics in coronary patients: differences between acute and one-month chronic dosing.

The pharmacokinetics of amiodarone (A) and its desethylamiodarone metabolite (DEA) were compared in the same coronary patients after a first 1000 mg dose and one-month chronic oral dosing. Terminal half-life (t1/2 el) of amiodarone increased from a mean (SD) 24.1 +/- 19.5 h after the first dose to 20.4 +/- 4.8 days after the last dose. Desethylamiodarone slowly appeared in the plasma after the first oral dose and its apparent t el was 61.6 +/- 26.6 h. After one-month dosing apparent t1/2 el of desethylamiodarone increased to 29.5 +/- 9.7 days. Mean maximal plasma amiodarone/desethylamiodarone concentration ratio decreased from 9.2 +/- 5.0 to 2.0 +/- 0.6 after chronic dosing. This change was mainly related to an increase in the plasma concentration of desethylamiodarone. These data suggest that after long-term treatment with amiodarone, the complete elimination of the drug and its metabolite may need 3-4 months in some patients. The results of this study were presented in part at the meeting of the Societe Francaise de Therapeutique et de Pharmacologie Clinique, Paris, December 1985.

Administration, Oral↗
PubMedDate not supplied

Influence of aspirin on the hemodynamic effects of sublingual nitroglycerin.

We studied the possible interaction between aspirin and nitroglycerin (NTG) in seven healthy volunteers. Effects of NTG (0.8 mg sublingual spray) were assessed by the decrease in diastolic arterial pressure, increase in heart rate, and decrease in M-mode echocardiographic end-diastolic and end-systolic diameters of the left ventricle. Measurements were performed before and during 30 min after NTG. Plasma levels of NTG were monitored during the experimental procedure. Each of the following trials was repeated three times, in random order, in each volunteer: NTG without aspirin pretreatment, NTG 1 h after 1 g of oral aspirin, and NTG after 8 days of aspirin, 500 mg every 48 h. Aspirin at the 1-g dose level significantly increased the effects of NTG on diastolic blood pressure (p less than 0.05) and left ventricular end-diastolic (p less than 0.001) and end-systolic (p less than 0.001) diameters. Aspirin (1 g) significantly increased (p less than 0.01) mean NTG plasma levels from 0.24 +/- 0.13 ng . ml-1 (control) to 0.37 +/- 0.26 ng . ml-1. We conclude that pretreatment with 1 g of aspirin increases NTG plasma levels and therefore significantly enhances the pharmacodynamic effects of NTG.

Adult↗
PubMedDate not supplied

Phenytoin monitoring in status epilepticus in infants and children.

Two successive protocols of phenytoin (PHT) plasma concentration monitoring were tested in 60 children with status epilepticus (SE). In each protocol, a loading dose of 15 mg/kg was injected and followed by three injections during the first 24 h. Clinical evaluation was performed at the end of the study by grouping patients into three classes according to seizure frequency during treatment: complete effect, partial effect, and no effect. In protocol 1, a complementary dose at the fourth hour was adjusted from individual plasma concentrations. Plasma concentrations at the 40th hour were within the therapeutic range in the 19 patients with complete effect (CE, mean 19 mg/L) and in the 5 patients with no effect (NE, mean 23 mg/L) whereas in the 11 patients with partial effect (PE), plasma concentrations were higher (mean 31 mg/L). In protocol 2, we added monitoring of the doses injected at the 16th and 24th hours to prevent the increase in PHT concentration noted in protocol 1. All patients but 1 were classified as either CE (13 patients) or NE (4 patients). In NE patients, average plasma concentration at the 40th hour (mean 10.5 mg/L) was lower than in CE patients (mean 15.7 mg/L). In both protocols, the NE patients were the youngest. In SE, PHT doses should be adjusted according to plasma concentrations to avoid overdosage and paradoxical inefficacy. Younger children had lower concentrations and appeared to respond less well than older children, but the etiology of SE may also play an important role.

Adolescent↗
PubMedDate not supplied

Effect of growth hormone on caffeine metabolism in hypophysectomized rats.

Two groups of six male Sprague-Dawley hypophysectomized rats (operated on day 0), 8 weeks old, treated by sc tetracosactid (ACTH, 10 micrograms every 24 hr), thyroxine (5 micrograms/100 g every 24 hr) and desmopressin (240 ng/kg/24 hr continuous infusion) received SC either saline (group I) or human growth hormone (hGH, 120 micrograms/24 hr) (group II) continuous infusion. ACTH and thyroxine were administered on days 7-19 and desmopressin and hGH on days 8-19, after surgery. They received po caffeine 4 mg/kg as citrate salt on day 15. The 0-12, 12-24 and 24-48 hr urine samples were collected after caffeine administration. Caffeine and metabolites concentrations in urines were determined using HPLC. Effect on hGH on caffeine metabolism was assessed comparing group I and group II. In 0-48-hr urine, 1-methylxanthine (154 +/- 169 pmol/g) and 3-7-dimethyluric acid (5.57 +/- 19.3 pmol/g) in group II were significantly lower than in group I (391 +/- 340 pmol/g and 262 +/- 338 nmol/g, respectively) (p less than 0.05). Other metabolites (6-amino-5-(N-methyl formylamino)-1,3-dimethyluracil included) excretion was not altered. Total, N3-, N7- and N1-demethylation ratios on 0-48 hr urine were not modified by hGH treatment. However, demethylation ratios on 12-24 and 24-48 hr (N3 + N7 + N1) and on 24-48 hr urine samples (N3 and N7) were significantly reduced in group II (p less than 0.05) suggesting an increase in the rate of appearance of demethylated metabolites during hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Comparison of the fluoride bioavailability from two oral preparations of monofluorophosphate disodium in combination with various calcium salts].

We studied, in twelve healthy volunteers, the pharmacokinetics of inorganic fluoride and calcium variations in serum and urine, parathormone variations in serum after administration of two oral preparations containing 100 mg of disodium monofluorophosphate (13.2 mg F as element) with different calcium salts (500 mg Ca as element). Fluoride was estimated in serum and urine with an ion specific electrode. The fluoride bioavailability from two preparations is identical with an areas under the curve corresponding to 61.05 and 62.53 mumols.l-1 h (after deduction of physiological fluoride concentrations) and urinary fluoride excretion after 72 hours corresponding to 266.6 and 246.1 mumols. The plasma peak appearance is rapid (one hour) and similar. The significant increase of urinary Ca-Creat ratio (70 to 100%) is identical four hours after drug administration. In the same way, a significant and early decrease of intact PTH in serum, measured with chemiluminometric method, was observed from two drugs. From these observations we may conclude that the two preparations are biologically equivalent.

Administration, Oral↗