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Biomedical subjects

M L Orme

Publications and source records attributed to M L Orme.

At least 127 records · Page 7Linked to original sources
PubMed1978

The pharmacokinetics of tritiated ethinylestradiol in the rabbit.

The disappearance of ethinylestradiol from the blood of rabbits has been studied, following the intravenous administration of this steroid. The disappearance followed two exponentials, the first having a half life (t1/2) of 5.5 min and the second, apparently terminal exponential was also rapid (t1/2-69 min). The plasma clearance was 150 ml/min which suggests almost total clearance of this steroid during a single passage through the liver. Bile contained a significant concentration of EE conjugates and thus this steroid could undergo enterophepatic recirculations. A large oral dose of unlabelled EE, given prior to intravenous administration of tritiated EE, considerably altered the pharmacokinetics of the latter by saturating both phase one metabolism (changes of the steroid nucleus) and the secretion of conjugates into bile. It was not clear whether phase two metabolism (conjugation) was also saturated.

Animals↗
PubMed1978

First-pass effect of norethindrone in rabbits and rats.

The influence of the route of administration on the pharmacokinetics of the synthetic progestogen norethindrone was studied in the rabbit and rat. In the rabbit, the area under the curve (AUC) after oral administration was 54% of that after i.v. administration. In the rat, the AUC after administration into the hepatic portal vein was 32% of AUCi.v.; after oral administration the AUCoral was 13.7% of AUCi.v. and 57.6% of AUCportal. Therefore, in both the rabbit and rat norethindrone is subject to a first-pass effect. Using the technique of constant withdrawal of blood from the hepatic portal vein after drug administration into the gastrointestinal tract, it was shown the norethindrone is metabolized in the gut wall. Hence, in the rat at least, there are both intestinal and hepatic components of the overall first-pass effect. In addition, increasing the time of intraportal injection from 15 sec to 2 min (thereby reducing the rate of drug delivery to the liver) resulted in the AUC being reduced by 40%. Dose-dependent kinetics were observed with doses of norethindrone greater than 500 microgram/kg.

Administration, Oral↗
PubMed1977

May mothers given warfarin breast-feed their infants?

Warfarin was measured with a sensitive and specific method in the plasma and breast milk of 13 mothers. Less than 0-08 micronmol warfarin per litre (25 ng/ml) of breast milk was found in each instance. Seven of the mothers were breast-feeding their infants, in none of whom was warfarin detected in the plasma; furthermore, in three the British corrected ratio of the plasma was appreciably less than that of the mother and was within the expected range. We conclude that nursing mothers given warfarin may safely breast-feed their infants.

Adult↗
PubMed1977

Phenylbutazone: plasma concentrations and effectiveness in patients with rheumatoid arthritis.

Phenylbutazone in doses of 50, 100, 200 and 400 mg/day has been given for four periods of three weeks to seven patients with rheumatoid arthritis. The trial was double/blind and the order of administration of the doses was arranged to eliminate order and carry-over effects. Before and at the end of each period the patient's clinical state was assessed by measurement of the pain score, duration of morning stiffness, paracetamol tablet count, grip strength, digital joint size, articular index and overall patient preference. The plasma phenylbutazone concentration was measured by gas liquid chromatography and the expected concentration of phenylbutazone in plasma was also predicted from a knowledge of the antipyrine half-life in each patient. Phenylbutazone had a significant therapeutic effect, in some cases after only 50 mg/day. There was however no correlation between the plasma concentration of phenylbutazone and its therapeutic effect. The observed plasma concentration of phenylbutazone agreed well with that predicted at doses of 50 and 100 mg/day. However, at 200 and 300 mg/day the observed plasma concentration was significantly lower than that predicted, perhaps due to saturation of the protein binding sites.

Adult↗
PubMed1976

Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. II. Relationship to its effect on blood pressure and plasma renin activity.

The kinetics of alprenolol, in relation to its effect on blood pressure and plasma renin activity, have been studied in sixteen patients. A within-patient comparison was made between therapy for six weeks with placebo or alpronolol 200 mg thrice daily. Thirteen patients responded to alprenolol by a signoficant fall in blood pressure. In three other patients treatment did not lower blood pressure. In the group as a whole there was no significant correlation between the fall in systolic, diastolic or mean blood pressure, and the steady-state plasma alprenolol concentration, renin status, or degree of beta blockade. However, the thirteen responsive patients showed a significant relationship (p less than 0.05 - 0.001) between the log mean steady-state plasma alprenolol concentration and the hypotensive response.

Adult↗
PubMed1973

Immediate decrease by hydrocortisone of the plasma half-life of antipyrine.

Infusion of hydrocortisone in man caused an immediate shortening of the plasma half-life of antipyrine. There was no change in the 'apparent' volume of distribution of antipyrine and the plasma concentrations of hydrocortisone during the infusion remained within physiological limits. Similar changes in plasma half-lives of antipyrine were observed in the dog, but in vitro studies of drug oxidation with dog liver failed to show any difference between biopsy samples taken before and during steroid infusion.Many drugs and chemicals are known to stimulate rates of drug oxidation in both man and animals. Administration of these inducing agents results in an increase in the activity of enzymes catalyzing drug oxidation, most of which are located with-in the endoplasmic reticulum of liver cells. In man there is usually a delay of 4-8 days before an appreciable change in rates of drug metabolism is seen when such an agent is administered (Breckenridge, Orme, Thorgeirsson, Davies & Brooks, 1971); in rats, the administration of enzyme-inducing agents causes increased rates of drug metabolism only 24-48 h after their administration.We wish to report in this paper an immediate and hitherto undescribed effect of hydrocortisone on rates of antipyrine elimination in man.

Adult↗