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Biomedical subjects

G Olive

Publications and source records attributed to G Olive.

At least 73 records · Page 4Linked to original sources
PubMed1989

Pharmacokinetics of intravenous salbutamol in renal insufficiency and its biological effects.

Salbutamol was administered intravenously to 5 patients with renal function impairment for estimation its pharmacokinetic parameters. The mean terminal half-life was 256 min, similar to previously reported values in healthy adults. The mean clearance (167 ml/min) and the mean volume of distribution (551) were decreased. These parameters were not correlated with the creatinine clearance. A slight but significant decrease was observed in the plasma potassium level up to 125 min after the salbutamol infusion. The heart rate was significantly increased, and the increase in 3 patients was correlated with the salbutamol concentration. The biological effects of the drug were less marked than expected.

Acute Kidney Injury↗
PubMed1989

Zolpidem excretion in breast milk.

Five, lactating, healthy white women were treated with a single 20 mg tablet of zolpidem 3-4 days after the delivery of a full term baby. The drug was administered at 20.00 h, 30 min after dinner, and milk samples were collected before and 3, 13 and 16 h. Venous blood 5 ml was taken before and 1.5, 3, 13, 16 h after zolpidem administration. The apparent elimination half life, estimated from plasma zolpidem concentrations was 2.6 h. The amount of zolpidem excreted in the milk at 3 h ranged between 0.76 and 3.88 micrograms, which represented 0.004 to 0.019% of the administered dose; no detectable (below 0.5 ng/ml) zolpidem was found in the milk at subsequent sampling times. The ratio of the zolpidem concentrations in breast milk and plasma at 3 h was 0.13. The apparent breast milk clearance of zolpidem, calculated from the ratio of the total amount of zolpidem excreted in milk to its AUC in plasma was 1.48 ml/h. The results show that the excretion of zolpidem in human milk is very low (below 0.02%) and that most of it takes place during the first 3 h following drug intake.

Adult↗
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↗
PubMed1989

[Use of the labelling of drugs with stable isotopes in clinical pharmacology in children].

There are only few studies available in the literature, using drugs labelled with stable isotopes in pediatric clinical pharmacology. However, the stable isotope methods are of great potential interest. These sensitive methods allow to quantitate drugs in small volumes of biological fluid with great specificity. They are innocuous and allow in vivo drug metabolic studies. Using 1-3 15N, 2 13C labelled theophylline, it has been possible to demonstrate N7-theophylline methylation into caffeine in premature neonates while this metabolic pathway is virtually not existent in adults. Stable isotope techniques allow to study intraindividual changes in kinetic parameters of drugs during maintenance therapy without discontinuing the drug. For instance, auto-induction of carbamazepine metabolism was demonstrated in children using stable isotope-labelled carbamazepine in serial pharmacokinetic studies during maintenance therapy. They also make bioavailability studies possible in children. These methods make possible new non invasive studies like CO2 breath test. Using 1-3-7 13C-caffeine we demonstrated the feasibility of the CO2 breath test in young infants and described the maturation of the N-demethylation pathway for caffeine. The correlation between the rate of 13C-CO2 elimination and caffeine plasma clearance indicates that the CO2 breath test is a non invasive method useful for measuring caffeine N-demethylation and that this test might theoretically be used for monitoring caffeine treatment.

Child↗
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 cimetidine on the pharmacokinetics of the new beta-blocker betaxolol.

The effect of cimetidine on the new beta-blocker betaxolol (Kerlone) was investigated in 7 healthy volunteers. Propranolol was used as a reference beta-blocking drug. In the control study, a single oral dose of propranolol (80 mg) was given (D0) followed by 5 daily doses of cimetidine (1 g) (D1-D6) and a second oral dose of propranolol (D7). The study was repeated with 20 mg of betaxolol replacing the propranolol dose. The oral clearance of propranolol was significantly decreased (21%). No significant effect of cimetidine on the kinetics of betaxolol was observed.

Adrenergic beta-Antagonists↗
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↗