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Biomedical subjects

J G Kelly

Publications and source records attributed to J G Kelly.

At least 73 records · Page 4Linked to original sources
PubMed1982

Pharmacokinetics of low-dose methotrexate in children receiving maintenance therapy for acute lymphoblastic leukaemia.

Serum methotrexate (MTX) concentrations were measured by immunoassay in 28 children receiving maintenance therapy for acute lymphoblastic leukaemia. Patients were studied either after a single weekly dose or on the first day of a 5-day course of treatment. A standard dose (15 mg/m2) was given PO and/or IV. After PO dose the peak serum MTX concentration and its timing varied widely between cases and there was a significant positive correlation between the rate of serum concentration rise and the area under the concentration curve up to 4 h. The absorption rate constant showed a biphasic distribution and correlated less closely with early serum concentrations. After IV and PO administration drug disposition was triphasic with an initial rapid distribution phase, an intermediate phase, and a prolonged terminal elimination phase. The intermediate phase half-life was significantly longer after PO than after an IV dose. The MTX clearance rate was consistently lower than the glomerular filtration rate and there was no significant correlation between the two. The mean bioavailability (PO/IV) was 42%, but bioavailability was as low as 6% in some cases due to prolonged high serum concentrations after an IV dose, which was not seen with the equivalent PO dose.

Administration, Oral↗
PubMed1982

The clinical pharmacology of tolmesoxide. A new vasodilator antihypertensive agent.

The haemodynamic response and pharmacokinetics of single dose oral tolmesoxide were studied at various dose levels in 4 patients with severe hypertension. There was a reproducible fall in mean arterial pressure from baseline of 24.2% and a rise in heart rate of 37.6% following administration of tolmesoxide. The onset of antihypertensive action occurred within 1 h, with a peak effect at 3 h after dosing. The mean duration of action was up to 12.0 h. Tolmesoxide had a mean half-life of 3.0 h. It was rapidly absorbed with a mean peak plasma level occurring at 1.0 h. Plasma levels correlated well with the doses administered. Side-effects include mild nausea, facial flushing and postural symptoms.

Aged↗
PubMed1982

Bioavailability of labetalol increases with age.

The antihypertensive drug labetalol was administered orally and intravenously to ten hypertensive patients aged between 28 and 75 years. There was a significant increase with age in both bioavailability and half-life of labetalol. Clearance tended to be lower in the elderly subjects. First pass metabolism results in variable oral bioavailability of labetalol which is greater in the elderly and this should be borne in mind when using the drug in this age group.

Adult↗
PubMed1981

Clinical pharmacology of tolmesoxide in refractory heart failure.

The haemodynamic effects and pharmacokinetics of single intravenous doses of tolmesoxide, a new vasodilator agent, were studied in 6 patients with severe cardiac failure secondary to ischaemic cardiomyopathy and refractory to conventional therapy. The mean (+ SEM) baseline cardiac index (CI) and pulmonary artery diastolic pressure (PADP) were 1.7 +0.11/min/m2 and 30.5 +4.1 mm Hg respectively. The mean % rise in CI was 78.8 +23.3 and the mean % fall in PADP was 35.2 +5.2. The mean half life of tolmesoxide in these patients was markedly prolonged at 15.6 +6.6h. Side effects were minimal - vomiting was seen in 1 patient. This agent warrants further study in the long term management of refractory cardiac failure.

Adult↗
PubMed1980

Digoxin "receptors" in neonates: an explanation of less sensitivity to digoxin than in adults.

To investigate the possibility of altered digoxin receptor binding properties in neonates, we compared digoxin binding with erythrocytes from neonates and adults. Neonatal erythrocytes had two and a half times as many digoxin binding sites as adult erythrocytes. The neonatal "receptors" also had dissociation constants for digoxin that were twice the adult value. These findings suggest that differences in binding properties may explain the clinical observation of decreased sensitivity to digoxin in neonates and infants.

Adult↗
PubMed1980

Effects of thyroid dysfunction on propranolol kinetics.

Propranolol kinetics was studied in six hyperthyroid and six hypothyroid patients who received single oral and intravenous doses of propranolol when they had thyroid dysfunction and again when they had become euthyroid. Change in thyroid status from hyperthyroid to euthyroid produced no change in the elimination half-life (t 1/2) of oral propranolol (3.2 +/- 0.5 to 4.1 +/- 0.7 hr), the oral clearance (38.4 +/- 7.3 to 27.4 +/- 2.4 ml/min/kg), the elimination t 1/2 of intravenous propranolol (2.5 +/- 0.3 to 3.5 +/- 0.7 hr), and the apparent volume of distribution (4.8 +/- 0.4 to 3.8 +/- 0.5 l/kg). The systemic clearance of propranolol, however, was greater when the patients were hyperthyroid (20.8 +/- 2.5 ml/min/kg) than when they had become euthyroid (11.7 +/- 1.7 ml/min/kg). The elimination t 1/2 after oral propranolol was longer in the hypothyroid (3.7 +/- 0.5 hr) than in the euthyroid state (2.0 +/- 0.1 hr). No other changes were observed in the kinetic parameters measured when these hypothyroid patients had become euthyroid. Adequate beta-adrenoceptor blockade in hyperthyroid patients may require higher propranolol dosage than expected.

Adult↗
PubMed1980

Theophylline kinetics in relation to age: the importance of smoking.

1 Single dose studies of theophylline kinetics were compared in groups of young and elderly smokers and non-smokers to assess the effect of age on theophylline absorption and the effect of smoking on drug metabolising enzyme activity in old age. 2 The rate and extent of absorption was not affected by age. Distribution and elimination kinetics were similar in young and elderly non-smokers. 3 In young subjects the elimination half-life of theophylline was shorter and clearance was significantly greater in smokers than in non-smokers. 4 In the elderly mean elimination half-life was significantly shorter in smokers and their plasma clearance was 40% higher than in non-smokers. The statistical difference for clearance was at the 7% level of significance. 5 These data indicate that ageing per se does not affect theophylline elimination and also that induction of theophylline metabolism due to smoking occurs in old age. Smoking is a variable that should be taken account of when assessing drug metabolism in elderly patients.

Absorption↗
PubMed1980

The clinical pharmacology of vasodilator antihypertensive drugs.

Vasodilator antihypertensive agents are defined and classified according to their mechanism and site of action. The effects of minoxidil, in combination with propranolol and a diuretic, on renal blood flow and renal function were studied following acute and chronic therapy. Although renal blood flow is reduced after two weeks on minoxidil, renal blood flow and renal function are not compromised after one year. The haemodynamic effects and pharmacokinetic profile of acute dosing with tolmesoxide, a new vasodilator antihypertensive agent are described. Results suggest that the long-term efficacy and safety of this drug are worth studying.

Antihypertensive Agents↗