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Biomedical subjects

L Hary

Publications and source records attributed to L Hary.

At least 19 recordsLinked to original sources
PubMed2003

Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects.

OBJECTIVES: Although the existence of a deep compartment for metformin has long been hypothesized, there is still little direct information concerning metformin distribution in individual tissues in man. The only available study involves chronic metformin therapy. In that study, the measurement of metformin in erythrocytes provided a reliable indicator of metformin distribution and of potential accumulation. To determine the kinetics of metformin in plasma and in erythrocytes after acute oral administration, we performed the present study in healthy subjects after a single oral dose of metformin and compared the pharmacokinetics parameters in erythrocytes to those in plasma. METHODS: Six nondiabetic participants took the study dose of 850 mg metformin at 8: 00 AM after a non-standardized breakfast (i.e., as recommended in clinical practice). Blood samples were collected for metformin measurement in plasma and in erythrocytes at 0, 1, 2, 3, 4, 6, 9, 24, 33, 48, 57, and 72 h. RESULTS: Maximum metformin concentration was attained at 3.0 +/- 0.3 h in plasma and 4.7 +/- 0.5 h in erythrocytes. This difference was not significant. Metformin concentrations peaked at a maximum almost 6 times higher in plasma than in erythrocytes (1.7 +/- 0.1 and 0.3 +/- 0.0 mg/l, respectively). However, because the elimination half-life of metformin was much longer in erythrocytes (23.4 +/- 1.9 h vs. 2.7 +/- 1.2 h), there was no difference in area under the curve between plasma and erythrocytes. The distribution volume (plasma) was calculated to be 146 +/- 11 l. Plasma and erythrocytes concentration-time curves showed that metformin was not detectable in plasma 24 hours after the oral administration, while it remained detectable in erythrocytes up to 48 hours. Metformin concentrations crossed approximately 13 hours after having reached their maximum values in plasma, approximately 16 h after metformin intake. CONCLUSION: Having demonstrated the rapid elimination of metformin from plasma and its slow disappearance from erythrocytes, the presents results should contribute to adjustment of metformin dosage to renal function, assessment of drug compliance, and retrospective analysis (when blood samples are drawn with delay) of the link between metformin and development of lactic acidosis. Most importantly, the present findings should help to ascertain the optimal dosage of metformin, particularly in elderly patients.

Adult↗
PubMed2001

Pancreatic concentrations of cefepime.

The concentrations of cefepime in pancreatic pseudocyst fluid (n = 4), pancreatic tissue (n = 4) and pancreatic fistula fluid (n = 1), and simultaneous plasma concentrations, were measured after intravenous administration of a single 2 g dose to nine patients. Mean plasma concentration was 27.4 mg/L between 120 and 200 min after the end of infusion. Mean pancreatic cefepime concentration was 6.3 mg/L in pseudocyst and 10.7 mg/L in pancreatic tissue. Cefepime was detected by 30 min after the end of the perfusion in pancreatic fistulae fluid, and persisted at 8 h. We conclude that cefepime is a potentially useful antibiotic in prevention and treatment of pancreatic infection.

Adult↗
PubMed1997

Serum bupivacaine concentrations and transplacental transfer following repeated epidural administrations in term parturients during labour.

Bupivacaine is the most widely used local anaesthetic in obstetrics for epidural analgesia. Nineteen women (mean age 26.9 +/- 5.3 years) who underwent epidural analgesia during labour were included in this study. All parturients received a first injection of 21.8 +/- 2.5 mg 0.25% plain bupivacaine. The following administrations were given on request: 0.25% concentration was used when cervix uteri was supple, and a 0.375% concentration when it was tonic. Blood samples were collected 5 min after the first injection and then every 30 min until delivery. At delivery blood samples were collected from the infant umbilical cord vein and from the arm vein of the mother. Bupivacaine was assayed by high pressure liquid chromatography. Serum data were analyzed for each patient using a non-compartmental model. Bupivacaine was rapidly detected in serum, and maximal concentration was reached between 5 and 35 min. Pharmacokinetic parameters were estimated in 17 women after the first injection: 87 +/- 35 min for elimination half-life, 60 +/- 19 L for apparent volume of distribution and 0.5 +/- 0.3 L/min for plasmatic clearance. For a mean total duration of labour and total dose administered of respectively 222 +/- 115 min and 57.1 +/- 28.7 mg the mean value of the foeto-maternal ratio was 0.29 +/- 0.10. The infant maximal serum concentration was 0.26 microgram/mL. No side effects were spontaneously reported by the parturients and all infants had an Apgar score of 10 at 5 min after the delivery. We confirm the fast systemic absorption and rapid elimination of bupivacaine which may be used without risk of acute toxicity both in mother and child, even when it is used in a 0.375% concentration.

Adult↗
PubMed1993

Lack of effect of magnesium-aluminium hydroxide on the absorption of theophylline given as a pH-dependent sustained release preparation.

Antacids can modify the pharmacokinetic parameters of sustained-release preparations of theophylline by changing the gastric pH. Though this has been studied with various theophylline/antacid combinations, the specific preparations investigated here have not previously been tested. The objective of the study was to assess any change in the availability of theophylline from a sustained-release preparation (SR), induced by the coadministration with an antacid. The study was designed as a double-blind randomized crossover trial in the Pneumology Departments of three general hospitals. Fifteen patients were studied. They all had stable asthma treated with theophylline and no major organ failure or gastro-intestinal lesions requiring the use of antacids. The antacid (aluminium hydroxide 800 mg and magnesium hydroxide 800 mg), or placebo, tid, was added to a stable regimen of theophylline SR bid, for 4 days, in crossover fashion. Plasma theophylline concentrations were measured before and 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h after the morning dose of Armophylline on the fourth day of each treatment period; the maximum plasma concentration (Cmax), and time to Cmax (tmax) were noted, and the area under the 24-h time-concentration curve (AUC0-24) and mean plasma concentration (Cmean) were computed. Peak expiratory flows on the same day, before and 3, 6 and 12 h after the morning dose of Armophylline were also measured. There was no change in any of the parameters studied. The addition of the antacid to theophylline, each given according to standard clinical practice, did not modify the pharmacokinetics of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

ACTH secretion from isolated hypophysial anterior lobes of male and female newborn rats: effects of corticotrophin-releasing factor, arginine vasopressin and oxytocin alone or in combination.

ACTH release by the anterior pituitary lobes of 8-day-old newborn rats (males and females) in the presence of rat corticotrophin-releasing factor (rCRF), arginine vasopressin (AVP) and oxytocin, given alone or in association, was measured in vitro. Rat CRF and AVP induced a dose-dependent release of ACTH in both sexes, while oxytocin was unable to stimulate ACTH secretion except at the highest dose tested. No sex-related difference was noted for any of the responses. Oxytocin (1 nmol/l) potentiated the response to rCRF (0.20 nmol/l) by the anterior pituitary lobes of females but not by those of males. This oxytocin potentiation was abolished when female newborn rats were injected at birth with testosterone (1 mg). AVP (1 nmol/l) alone stimulated ACTH release from the anterior pituitary lobes of the newborn rats of both sexes and markedly potentiated the ACTH response to rCRF. Although no difference between the sexes was noted for basal levels of AVP and oxytocin in the hypothalamus, the neurointermediate lobe and the peripheral plasma, the present data on the sex-related effect of oxytocin on the newborn adenohypophysis could, in part, explain why ACTH release in response to ether stress was previously reported to be more lasting in females than in males on day 8 postpartum.

Adrenocorticotropic Hormone↗
PubMed1991

Pharmacokinetics and ascitic fluid penetration of piperacillin in cirrhosis.

The pharmacokinetics of piperacillin were evaluated in seven healthy volunteers, eight cirrhotic patients without ascites and 11 cirrhotic patients with sterile ascites after a single 15-min intravenous infusion of 4 g of the drug. In ascitic patients, piperacillin rapidly entered the peritoneal fluid. Peritoneal concentrations were higher than 10 mg/l from 0.5 to 8 h after the infusion. Disappearance rate of piperacillin was slower in the ascitic fluid than in plasma. The plasma half life of piperacillin was more prolonged in cirrhotic patients that in control subjects. This difference was more marked in ascitic patients for whom half life was twice as high as in volunteers (1.95 versus 0.91 h; P less than 0.01).

Adult↗
PubMed1991

Pharmacokinetics of single-dose intravenous, oral, and intraperitoneal pefloxacin in patients on chronic ambulatory peritoneal dialysis.

Comparison of plasma and dialysate concentrations of pefloxacin after intravenous, oral, or intraperitoneal administration shows excellent bidirectional diffusion of the quinolone through the peritoneal membrane, demonstrating that therapeutical concentrations can be achieved in the dialysate after intravenous or oral administration. In this study, the half-life of the drug was 18.8 +/- 1.4 h, i.e., apparently longer than that reported for normal controls or uremic patients on hemodialysis.

Administration, Oral↗
PubMed1990

Type 2 diabetes in the elderly: an assessment of metformin (metformin in the elderly).

Metformin efficacy and safety in type 2 diabetes has not been studied in the elderly patient under conditions pertaining to clinical practice. We have therefore, studied prospectively over two months 24 patients aged between 70-88 years with 115% mean ideal body wt and glycemic control greater than 10 mol.l-1 fasting and/or greater than 14 mol.l-1 postprandial, and/or an HbA1 value greater than 10%. At entry into the study, patients were on metformin + sulfonylurea (n = 15), sulfonylurea (n = 3), metformin (n = 2), insulin (n = 1) or diet alone (n = 3). They received metformin as the sole therapy when possible (sulfonylureas were discontinued in 9 cases) at a dosage of either 850 mg or 1,700 mg/day dependent on creatinine clearance values of 30-60 ml.min-1 (n = 11) and greater than 60 ml.min-1 (n = 13), respectively. Compared to pretreatment values, glycemic control at 1 and 2 months were unchanged, with metformin blood levels remaining within expected values for both dosage groups. Blood lactate levels remained unchanged in the high dosage group but were reduced (p less than 0.05) on 850 mg/day probably because of the reduction of metformin dosage in patients already treated prior to the study. It is concluded that provided the dosage is adjusted to renal function, the metabolic tolerance of metformin therapy is satisfactory in the elderly type 2 diabetic patient. With regard to efficacy, longer observations are needed to know whether this therapy may offer on a long-term basis equivalent glycemic control compared to other treatment modalities.

Aged↗
PubMed1989

The pharmacokinetics of ceftriaxone and cefotaxime in cirrhotic patients with ascites.

We have compared in two separate studies the kinetics of ceftriaxone and cefotaxime in 8 cirrhotic patients with ascites and 8 control subjects after a single 20 min intravenous infusion of 1 g of each drug. The apparent volumes of distribution (Vz) were found to be significantly higher in cirrhotics than in control subjects (0.87, versus 0.49, l.kg-1, for cefotaxime and 0.23 versus 0.13 for ceftriaxone). The elimination kinetics of ceftriaxone were similar in the two groups. In contrast, the total and non-renal clearances of cefotaxime were reduced in cirrhotic patients. The two drugs rapidly entered the ascitic fluid. Peritoneal concentrations of ceftriaxone were higher than 7 micrograms.ml-1 from the second hour after the infusion and were 8.9 micrograms.ml-1 at 24 h. Peritoneal concentrations of cefotaxime were higher than 4 micrograms.ml-1 from 0.5 to 8 h after the infusion.

Ascites↗
PubMed1988

[Clinical and pharmacokinetic study of ceftriaxone in the treatment of 14 episodes of ascitic fluid infection].

A clinical study and dosages of ceftriaxone were performed during the treatment of 14 ascitic fluid infections. Fourteen cases of ascitic fluid infection were treated with ceftriaxone at doses of 2 grams daily. The isolation of the causative organisms was obtained in 11 out of 14 cases by systematic culture of the ascitic fluid in hemoculture bottles with aerobic and anaerobic medium. Of 11 evaluable infectious episodes ten were cured. Ceftriaxone diffuses rapidly in the ascitic fluid because, within the first hour; mean concentrations were already of 18.6 micrograms/ml largely exceeding the usual MIC for these organisms. A good tolerance for the drug, the well spaced rythm of infections preventing unnecessary parenteral treatment in cirrhotic patients, and its effectiveness against Enterobacteriaceae justify its choice in the treatment of ascitic fluid infections with sensitive organism.

Aged↗
PubMed1988

[Consequences of ischemia of the terminal ileum in the rat: influence of exclusive parenteral nutrition].

An experimental model of ischemia of the distal part of the small intestine has been realized in rats. This experimental study realizes a moderate ischemia of the distal part of ileum loops, by vascular ligations. An important decreasing of the intestinal motility is observed 2 days after the operation, by in vitro study. The motility became normal 7 days after. During this time a microbiological evaluation revealed an important increasing of anaerobic germ in the distal ileum. Total parenteral nutrition preserves the intestinal motility and the endoluminal flora. Ischemia of the small bowel is an important component of enterocolitis by modification of the peristalsis. The total Parenteral Nutrition in such condition seems to protect the intestinal flora.

Animals↗
PubMed1987

Diltiazem increases steady state digoxin serum levels in patients with cardiac disease.

Diltiazem has been reported to decrease or not to affect digoxin elimination. The effects of diltiazem on steady state concentrations of digoxin was evaluated in eleven patients with congestive heart failure receiving this drug for at least two weeks. The mean trough digoxin was 1.11 +/- 0.18 ng/ml before the coadministration of diltiazem (180 mg/day). This concentration increased to 1.54 +/- 0.22 ng/ml after three days and to 1.54 +/- 0.23 ng/ml after seven days of coadministration (P less than 0.01). Clinically, no patient showed signs of digitalis toxicity. Creatinine clearance was unchanged. The present results show that when diltiazem is added to a regimen that includes digoxin, steady state concentrations of this glycoside may increase.

Adult↗
PubMed1987

[Perinatal influence of sex hormones on the differential activation of corticotrope function during stress in the male and female].

The stress-induced activation of the corticostimulating function of the pituitary gland was noted to vary according to sex in both the adult and the newborn. The pituitary response in testosterone or estradiol-injected females at the time of birth was similar to that of intact males, in contrast, the castration of the males performed just before the postnatal surge of plasma testosterone was unable to modify at the 8th day, the male characteristic evolution in response to ether inhalation. Present data suggest--in the male, prenatal differentiation of the neuroendocrine pathways involved in the pattern of ACTH release in response to ether inhalation, probably in correlation with the peak of plasma testosterone on day 19 of gestation--in the female, the existence of androgen--sensitive structures in early postnatal life. An alpha stimulatory effect of norepinephrine on these neuroendocrine pathways was suggested. Present report also discuss--the catecholaminergic control of CRF X producing neurons--the sex dependent AVP and/or oxytocin (OT) release induced by a stress--the AVP and OT potentiation of CRF-induced ACTH release.

Adrenocorticotropic Hormone↗
PubMed1986

Enhanced dopamine renal responsiveness in patients with hypertension.

The purpose of the study was to compare the renal effects of low doses of exogenous dopamine to assess the responsiveness of renal dopaminergic receptors in normotensive and hypertensive subjects. Eight hypertensive patients and seven normotensive volunteer subjects were studied. Inulin and para-aminohippuric (PAH) clearances, natriuresis, and fractional excretion of sodium increased significantly after intravenous dosing with dopamine (2 micrograms/min/kg) in both groups. These increases were significantly higher in hypertensive than in normotensive subjects: 31.8% +/- 3.7% vs. 16.2% +/- 1.2% for inulin clearance (P less than 0.01), 83.3% +/- 10.5% vs. 41.1% +/- 3.4% for PAH clearance (P less than 0.01), and 331% +/- 38% vs. 216% +/- 26% for natriuresis (P less than 0.01). These findings suggest hyperresponsiveness to dopamine during hypertension. This enhanced response to exogenous dopamine can be considered as a further argument favoring the existence of a deficit in dopaminergic activity during hypertension. Dopamine also induced a significant reduction in blood pressure and increased heart rate in hypertensive subjects but no significant change in blood pressure and heart rate occurred in normotensive subjects.

Adult↗
PubMed1986

Effects of castration and testosterone on the pituitary and adrenal responses of the newborn rat to ether inhalation.

In 8-day-old rat newborns, the pituitary response to 2 min of ether inhalation was noted to vary according to sex. Plasma ACTH levels were similarly increased in males and females at the end of ether exposure; however, during the following 30 min, ACTH levels were always higher in females than in males. In order to verify that the putative masculinization of some neuroendocrine pathways involved in the pituitary response to ether stress was the result of the transitory surge of testosterone at birth, fetuses at term were delivered by cesarean section and thereafter immediately castrated or sham-castrated under cold anesthesia (males), injected with testosterone heptylate (1 mg s.c.) or olive oil used as solvent (females) before being put in the care of a nurse. The rise in plasma testosterone levels during the 1st h after birth was prevented or stopped in males put at 2 degrees C. At the 8th postnatal day, the newborns were subjected to 2 min of ether inhalation; they were sacrificed either just, before or after the end (0 and 30 min) of the stress procedure. Plasma immunoreactive ACTH level and adrenal corticosterone content were measured. The pituitary response, shown by the ACTH increase, in castrated or sham-castrated males and testosterone-injected females was similar to that of intact males but very different from that observed in olive-oil-injected or intact females. The rise in adrenal corticosterone content 30 min after ether inhalation was greater in intact and olive-oil-injected females than in testosterone-injected ones or in males; adrenal response was well correlated with the maintenance of ACTH release in the former and the decrease following transitory surge in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

Effect of norepinephrine on the pituitary adrenocorticotrophic activation by ether stress and on the in vitro release of ACTH by the adenohypophysis of male and female newborn rats.

The effect of norepinephrine (NOR) has been investigated in 8-day-old newborn rats of both sexes subjected to stress by 2 min ether inhalation or sham stress. The animals were sacrificed either before or 2 and 32 min after the stress or the sham stress procedure was started. Investigations were also performed on newborns bearing neurotoxic lesions of the arcuate nucleus by neonatal treatment with monosodium-L-glutamate. The effect of NOR was also investigated in vitro on incubated pars distalis. ACTH concentrations in the pituitary, plasma, and the incubation medium were determined by radioimmunoassay. NOR at the dose of 0.2 microgram/g was unable to affect plasma ACTH levels during a period of 60 min in unstressed newborns, in contrast to higher doses (0.5, 1, and 5.0 micrograms/g) which elicited a sharp rise in plasma ACTH levels. Then, NOR was injected (0.2 microgram/g) to male and female pups 15 min before the stress or sham stress procedure. 32 min after the beginning of ether inhalation, the pituitary response was greater in NOR-injected than in saline-injected males; in NOR-treated females the rise in plasma ACTH levels was higher at 2 and 32 min than in saline-injected animals. At this latter time, plasma ACTH levels were similar in NOR-treated males and females, while in saline-treated newborns, the response to ether stress was greater and more longlasting in females than in males. No significant rise in plasma ACTH levels was observed in sham-stressed pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗