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Biomedical subjects

G Pons

Publications and source records attributed to G Pons.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Effect of pregnandiol on caffeine metabolism in female rats.

Three groups of six 5-week-old Sprague Dawley female rats received i.p. injections of pregnandiol, 1.25, 2.50 or 5 mg/kg, respectively, in triolein daily for 7 days. Caffeine metabolism was studied in liver slices on day 8 by HPLC. Only primary metabolites were formed. N-1 demethylation was the most important pathway (theobromine represented 51% of total dimethylxanthines). Unlike in human in vitro or in vivo, 1,3,7-DAU (6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil) was an important metabolite (9.7% of total caffeine metabolites). Pregnandiol inhibited N-1, N-3 and N-7 demethylation in vitro (-33%, -33% and -28%, respectively, at 5 mg/kg/day), but it had no effect on N-1 demethylation at 1.25 or 2.50 mg/kg/day. Pregnandiol at all doses had no effect on 1,3,7-trimethyluric acid and 1,3,7-DAU formation. These results are consistent with the hypothesis that C-8 hydroxylation and demethylation of caffeine are mediated by different isoenzymes. They indicate that pregnandiol is a potent inhibitor of microsomal drug metabolism, specifically of cytochrome P450 IA, which could explain the immaturity of some metabolic pathways of caffeine in neonates.

Animals↗
PubMedDate not supplied

Effects of transdermal nitroglycerin in children with congestive heart failure: a Doppler echocardiographic study.

The aim of this study was to evaluate by Doppler echocardiography whether administration of transdermal nitroglycerin (NTG) to children with congestive heart failure could modify mitral flow velocity profile with redistribution of left ventricular filling to late diastole, suggesting preload reduction of the left ventricle. Twelve children with congestive heart failure, aged from 6 months to 6 years (2.83 +/- 2.24 years; mean +/- SD), were recruited. Patients were randomly allocated either a NTG patch (study group; n = 6) or a placebo patch (control group; n = 6) in a double-blind procedure. The NTG patch was a 10-cm(2) patch releasing 5 mg of NTG per day. NTG patches were adjusted to a dose of 1 cm(2)/kg/day (0.5 mg/kg/day). Peak velocity and time--velocity integral (TVI) of E and A waves of transmitral flow, the ratio of the velocities of the A wave and E wave, and the ratio of the TVI of the A wave to the TVI of the E wave were measured. Doppler measurements were determined before treatment (H0) and 4 hours (H4) and 23 hours (H23) after the patch application. Relative changes of these parameters were not significantly different between these two groups. In the NTG group, mean NTG plasma concentration was 1.08 +/- 0.47 microg Liter(-1) at H4 (n = 5) and 1.18 +/- 0.81 microg Liter(-1) at H23 (n = 5). No patient had a NTG plasma concentration greater than 2 microg Liter(-1) either at H3 or at H24. These data suggest that 1 cm(2)/kg transdermal doses of NTG may have a limited bioavailability or a higher clearance and minimal hemodynamic effects in children with congestive heart failure already receiving other medications, implying that higher doses should be used.

Administration, Cutaneous↗
PubMedDate not supplied

[How to improve drug development and utilization in pediatrics].

Insufficient drug evaluation in children and the lack of adapted pharmaceutical formulations explain the importance of unlicensed and off-label prescriptions. As a consequence a regulation proposed in the USA by the Food and Drug Administration, requiring manufactures to assess the safety and effectiveness of new drugs in paediatric patients, has recently been adopted. Appropriate means to facilitate drug evaluation in children are now necessary in terms of recruitment and methodology. A ten-centre American Pediatric Pharmacology Research Unit network has been created and is being financed by the National Institute of Health. A similar trend is evolving in Europe. Appropriate drug utilization in children requires adequate formulations, administration devices and information as well as improved knowledge on the long-term potential consequences of drug use during growth and maturation.

Age Factors↗
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

[Optimal dose of acetaminophen in children].

Acetaminophen is an antipyretic and analgesic drug frequently prescribed in children. Unlike aspirin, the recommended doses for acetaminophen are different in France (20-30 mg/kg/24 h) and in the USA (65 mg/kg/24 h). The authors reviewed literature data, looking for the scientific basis of these recommendations in children. The antipyretic effect of a 7-20 mg/kg single oral dose was demonstrated versus placebo. A dose-effect relationship was established: 20 mg/kg as a single oral dose was more effective than 10 mg/kg while 5 mg/kg had little antipyretic effect. More than 10 mg/kg were required to keep on average the temperature 1.5 degrees C below the starting point for 6 hours. There was no significant difference regarding the antipyretic effects of a single 10-15 mg/kg dose using suppositories or oral suspension, although there was a greater consistency of response with the oral suspension. There was no significant difference concerning the antipyretic effect between a 10-15 mg/kg acetaminophen oral dose and the same dose of aspirin. The analgesic effect of a single 10-15 mg/kg oral dose was also demonstrated versus placebo in children. Plasma concentrations between 4 and 18 mg/l seem appropriate to obtain an antipyretic effect. Half-life is 1-3.5 h. Based on these data different dose regimens including an initial loading dose have been proposed. The simplest one is as follows: 25 mg/kg loading dose and 12.5 mg/kg every 6 h as maintenance dose.

Acetaminophen↗
PubMedDate not supplied

[Successful fibrinolytic treatment in a patient with acute mitral prosthetic thrombosis].

A case is described of a 50 year-old man with an acute prosthetic dysfunction due to valve thrombosis and cardiogenic shock, on a prosthesis in the mitral position (Bjork-Shiley). The patient was promptly treated with a streptokinase in two infusions 1.5 x 10(6) UI over 180 and 90 minutes, respectively. Early clinical, fluoroscopy and echocardiography improvement was observed. The authors comment the present role of the thrombolytic therapy in front of surgery of prosthetic valve thrombosis.

Acute Disease↗
PubMedDate not supplied

[A "low junction"].

Explore the source record for details and available documents.

Adult↗
PubMedDate not supplied

[Neonatal laryngeal paralysis. Course and treatment. 56 cases (author's transl)].

56 laryngeal paralyses were seen in newborn infants between 1970 and 1976 (25 bilateral, 31 unilateral). The aetiology was obstetric trauma in 11 cases, nuclear agenesis in 7 cases, a severe neurological disorder (spina bifida, hydrocephaly, microcephaly, lesions of the central nervous system) in 13 cases, and congenital heart disease in 3 cases. In 10 cases, the paralysis was present in isolation. The initial state was not recorded in 11 cases. The course varied according to the aetiology: 5 deaths, 4 due to the severity of neurological problems. Regression, which invariably occured before the end of the 6th month, was seen in all the cases with an obstetric aetiology and in 50% of those in which the paralysis was present in isolation. There was persistence in the majority of neurological, nuclear or central causes. However, subsequent tolerance of persistent forms was good in all those patients followed-up on a regular basis, apart from 5 who underwent surgery. Treatment consisted of intubation for forms poorly tolerated initially, for the first few weeks. Tracheotomy did not prove necessary in any case. 5 patients underwent surgery: arytenoidectomy or arytenoidopexy via an extralaryngeal approach.

Birth Injuries↗
PubMedDate not supplied

Caffeine metabolism in liver slices during postnatal development in rats.

The metabolism of caffeine was investigated in liver slices from newborn, preweanling, postweanling, and adult rats. All metabolites were identified and quantified by HPLC without using radioactive compound. Caffeine metabolism underwent dramatic changes during maturation in rats. The specific activity of the enzyme system was extremely low when liver slices from 1-day and 7-day-old rats were used. This capacity increased gradually with increasing age and reached a peak following weaning at 21 days of age. In rat liver slices, N-1 demethylation to theobromine was the main pathway of in vitro caffeine metabolism at all ages. Theobromine represented 25% of total caffeine metabolites at day 1 and about 40% at all others ages. 1,3,7-6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil is a minor metabolite in newborn (1-day-old), preweanling (7-day-old), and adult rats (120-day-old), but an important metabolite in postweanling rats. Conversely, 1,3,7-trimethyluric acid is a major metabolite in newborn and adult rats and a minor one in preweanling and postweanling rats. This liver slices model could be used as a simple and versatile model to study metabolism during maturation.

Animals↗
PubMedDate not supplied

Relevance of the pharmacokinetics of non-steroidal anti-inflammatory drugs (NSAIDs) in children.

The pharmacokinetics of the NSAIDs is relevant to therapy in different ways: absorption, protein binding and distribution, metabolism and elimination. The pharmacokinetics of a drug is most relevant to therapy when plasma concentrations of the drug are related to efficacy and/or to side effects. The kinetic parameters then allow one to calculate the optimal dose regimen, i.e. the one maintaining plasma concentrations within the therapeutic range. The pharmacokinetic characteristics of the different NSAIDs relevant to therapy in children are reviewed.

Absorption↗