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Biomedical subjects

A K Scott

Publications and source records attributed to A K Scott.

At least 37 records · Page 2Linked to original sources
PubMed1987

Hepatic enzyme induction and vitamin K1 elimination in man.

We have studied the effect of hepatic enzyme induction on vitamin K1 elimination in patients on long-term anticonvulsant therapy and in volunteers given rifampicin. Neither the anticonvulsants (phenytoin and phenobarbitone) nor rifampicin had any significant effect on vitamin K1 elimination half-life or AUC. The neonatal haemorrhage which occurs in babies born to mothers on long-term enzyme inducing drugs is unlikely to be related to an increased rate of vitamin K elimination in the mother.

Adult↗
PubMed1987

Sorbinil pharmacokinetics in male and female elderly volunteers.

Sorbinil pharmacokinetics were studied, following a single oral dose, in eight male and eight female healthy, elderly volunteers. Elimination half-life tended to be longer in males than in females. There was no sex difference in AUC or renal clearance. The long elimination half-life of sorbinil in the elderly suggests that accumulation is likely to occur with chronic dosing.

Aged↗
PubMed1987

Once daily amlodipine in the treatment of mild to moderate hypertension.

1. The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo controlled parallel group study. The dose range of amlodipine was 2.5-10 mg daily titrated at 2 weekly intervals for a total treatment period of 8 weeks. 2. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. 3. Blood pressure returned to baseline values during a terminal 4 week washout period on placebo. 4. There were no significant effects on heart rate. 5. Two patients experienced slight ankle oedema while receiving amlodipine 10 mg daily but the active drug was otherwise well tolerated. 6. Plasma concentration of amlodipine, sampled 24 h after the preceding dose, increased as the dose titration sequence was followed, averaging 2.5 ng ml-1 on 2.5 mg, 4.9 ng ml-1 on 5 mg and 10.5 ng ml-1 on 10 mg.

Adult↗
PubMed1985

Computer assisted shared care in hypertension.

A computer assisted shared care scheme for the long term management and follow up of hypertensive patients has been developed in the Grampian Region. The scheme aims at facilitating the exchange of clinically important information between doctors and at achieving target levels of blood pressure with treatment in patients at highest risk of cardiovascular events. The shared care scheme has been well received by the local practitioners. Two hundred and fifty seven patients (18%) of 1426 patients under current long term follow up are assigned to follow up in the hospital aspect of the scheme. At the most recent visit 32% of patients in the hospital aspect and 10% of 1169 patients in the general practice aspect had blood pressure recordings above the target levels of 160/95 mm Hg. The stratification of patients formerly attending hospital clinics into grades of risk has rationalised our follow up procedures to allow the specialist resources to be freed and concentrated on those patients at highest risk and with the most complex problems. This computer assisted patient records system could be applied to other groups of high risk patients in whom long term follow up and surveillance are necessary--for example, patients with diabetes mellitus--and has implications for optimising and monitoring the delivery and outcome of care without overwhelming limited hospital resources.

Computers↗
PubMed1985

A comparison of the pharmacokinetics of atenolol, metoprolol, oxprenolol and propranolol in elderly hypertensive and young healthy subjects.

Six elderly patients with established hypertension and six young healthy subjects were studied after 8 days of treatment with atenolol 50 mg day-1, metoprolol 50 mg day-1, oxprenolol 80 mg day-1 and propranolol 80 mg day-1. The area under the blood concentration-time curve was increased in the elderly group for each drug, but the difference was statistically significant only for atenolol. The lower serum albumin concentrations in the elderly group did not result in a decrease in the percentage of propranolol or oxprenolol bound to serum proteins.

Adrenergic beta-Antagonists↗
PubMed1985

Vitamin K1 metabolism in relation to pharmacodynamic response in anticoagulated patients.

The disposition of, and pharmacological response to, a single intravenous dose of vitamin K1 (10 mg) was studied in eleven patients on daily warfarin therapy. The pharmacokinetics of vitamin K1 in patients were similar to those reported previously in healthy volunteers, terminal half-life 1.7 h. All patients had been taking warfarin for at least 3 months. Steady state warfarin plasma concentrations ranged from 0.5 to 1.4 micrograms ml-1. Prothrombin complex activity ranged from 15 to 28.5%. There was considerable inter-individual variation in pharmacodynamic response as expressed by prothrombin complex activity (PCA) and Factor VII. The maximum values for PCA and Factor VII were reached at 24-96 h and 24-48 h, respectively, after the administration of vitamin K1. Vitamin K1 (10 mg) has a long duration of action (greater than 168 h) in terms of clotting factor synthesis in patients on steady state warfarin. All the patients on warfarin had measurable levels (CPmax 0.3-1.2 micrograms ml-1) of vitamin K1 2, 3-epoxide. There was a significant correlation between the pharmacodynamic response as expressed by change in % PCA and the AUC for vitamin K1 2,3-epoxide (P less than 0.05).

Adult↗
PubMed1985

A study of the relationship between the pharmacokinetics and the pharmacodynamics of the 4-hydroxycoumarin anticoagulants warfarin, difenacoum and brodifacoum in the rabbit.

The pharmacokinetics and pharmacodynamics of the 4-hydroxycoumarin anticoagulants, brodifacoum, difenacoum, and warfarin have been studied in the rabbit. Sensitive (50 ng ml-1) and specific high performance liquid chromatography assays have been developed for the determination of plasma concentrations of warfarin, brodifacoum and difenacoum. After administration of a single intravenous dose (20 mumol kg-1), plasma concentrations of warfarin underwent mono-exponential decay, with a terminal half-life of 5.6 +/- 0.7 h (mean +/- s.e. mean), whereas plasma concentrations of brodifacoum and difenacoum underwent bi-exponential decay with terminal half-lives of 60.8 +/- 1.9 h and 83.1 +/- 10.3 h respectively. The plasma half-life of brodifacoum in a single patient poisoned with the compound was 487 h. The pharmacological response to the anticoagulants was measured as changes in prothrombin complex activity, from which the rate of clotting factor synthesis was determined. Clotting factor synthesis recovered in a monophasic fashion after a single intravenous dose of warfarin, compared with a more complex biphasic, pattern of recovery of clotting factor synthesis after administration of either brodifacoum or difenacoum. The slope (m) of the intensity of effect-log (amount of drug in the body) curve was derived for each anticoagulant. There was no significant difference in the value of m after single intravenous doses of racemic, R-, and S-warfarin, difenacoum and brodifacoum, which is consistent with the hypothesis that all the 4-hydroxycoumarin anticoagulants produce their anticoagulant effect by acting at the same receptor site, vitamin K epoxide reductase. Determination of the minimum plasma concentration of each anticoagulant that corresponded with the complete inhibition of clotting factor synthesis indicated that racemic warfarin, R-warfarin and brodifacoum have similar potencies in the rabbit and are less potent than S-warfarin and difenacoum.

4-Hydroxycoumarins↗
PubMed1984

Interaction between warfarin and propranolol.

The interaction between propranolol and warfarin was investigated in six healthy volunteers using a low dose warfarin protocol and in New Zealand white rabbits. Warfarin concentration (Cmin) in the volunteers increased by 14.7% on addition of propranolol (P less than 0.02). There was no significant change in prothrombin time. In the rabbit study, elimination half-life was shorter in the propranolol treated animals (8.20 +/- 0.44 h) than in controls (10.89 +/- 0.62 h). This was due to a fall in its volume of distribution from 1.13 +/- 0.10 1 kg-1 in controls to 0.81 +/- 0.08 1 kg-1 in the propranolol treated group. Clearance was not significantly altered. The small change in warfarin concentration could be of clinical importance in some patients because warfarin has a low therapeutic index. This requires further investigation.

Adult↗
PubMed1984

Plasma disposition of vitamin K1 in relation to anticoagulant poisoning.

The disposition of vitamin K1, after intravenous (10 mg) and oral doses (10 mg and 50 mg) was studied in six healthy male subjects. After intravenous administration, the plasma concentration-time profile was adequately fitted with an average terminal half-life of 1.7 h. After oral administration (10 mg and 50 mg) the availability of vitamin K showed marked inter-individual variation (10-63%). With the higher dose intra-individual variation was also observed. Experiments in brodifacoum-anticoagulated rabbits demonstrate that the duration of action of a pharmacological dose (10 mg/kg) is short (9 h) and that high plasma concentrations (ca 1 microgram/ml) of the vitamin are required to drive clotting factor synthesis during maximum coumarin anticoagulation. Taken collectively, these data indicate that the short duration of action of vitamin K, frequently observed in cases of coumarin poisoning, is a consequence of requirements for high vitamin K concentrations and rapid clearance of the vitamin.

Adult↗
PubMed1984

Oxazepam pharmacokinetics in thyroid disease.

The pharmacokinetics of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in seven hyperthyroid and six hypothyroid patients before and after treatment. Oxazepam elimination half-life was shorter and apparent oral clearance higher in untreated hyperthyroid patients than after treatment. There was no significant change in oxazepam elimination in hypothyroid subjects. Time to peak concentration (tmax) was reduced in the hyperthyroid state. Hypothyroidism had no significant effect on tmax. Serum bilirubin concentration was lower in the patients while hyperthyroid before treatment than when euthyroid and also lower than in the hypothyroid patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. These results suggest that glucuronyl transferase activity is increased in hyperthyroidism but is not altered in most patients with hypothyroidism. The extent of increase in glucuronyl transferase activity is similar to that produced by enzyme inducing drugs.

Adult↗
PubMed1983

Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone.

The pharmacokinetics and serum protein binding of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in nine epileptic patients treated long-term with phenytoin or phenytoin with phenobarbitone, and in nine healthy control subjects. Oxazepam elimination half-life was shorter and apparent oral clearance higher in treated patients than in age and sex matched control subjects. Serum bilirubin concentration was lower in treated patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. Serum alpha 1-acid glycoprotein concentration was higher in the treated patients than in the control group. Oxazepam was more than 93% bound to serum proteins, but the extent of binding was not significantly different between the two groups. These results show that oxazepam glucuronyl transferase activity is increased by treatment with phenytoin alone or in combination with phenobarbitone in epileptic patients.

Adult↗
PubMed1982

Atenolol and metoprolol once daily in hypertension.

The effect of once-daily dosage of the two most widely prescribed cardioselective beta-adrenoceptor antagonists used to treat hypertension--namely, atenolol and metoprolol--was studied in nine carefully selected hypertensive outpatients. Each patient received atenolol 50 mg/day, atenolol 100 mg/day, metoprolol 100 mg/day, and metoprolol 200 mg/day in a sustained-release formulation (as Lopresor SR) according to a randomised sequence. After three weeks' treatment with each drug given once daily comparisons of the treatments 24 hours after dosing showed no important differences between 50 and 100 mg atenolol/day. Metoprolol, as both the standard and the slow-release formulations, had some limitations in controlling systolic blood pressure and heart rate. These results suggest that the recommendations for the treatment of hypertension with these cardioselective beta-adrenoceptor antagonists should be reconsidered since doses smaller than those recommended are almost as effective and much cheaper.

Adult↗
PubMed1980

Atenolol, sustained-release oxprenolol, and long-acting propranolol in hypertension.

The effect of once-daily atenolol, sustained-release oxprenolol (a new formulation of oxprenolol presented as a compressed tablet in a waxed matrix), and long-acting propranolol (a new formulation presented as spheriods in a capsule) was studied in a double-blind crossover trial in 23 carefully selected hypertensive outpatients. After a run-in period with matching placebo each patient received atenolol (100 mg/day), sustained-release oxprenolol (160 mg/day), long-acting propranolol (160 mg/day), and placebo according to a randomised sequence. After four weeks' treatment with sustained-release oxprenolol blood pressure in the two to four hours before the next dose was not significantly lower than after placebo. The effectiveness of atenolol and of the new formulation of propranolol in reducing blood pressure was confirmed. These results suggest that the present formulation of sustained-release oxprenolol should be reconsidered.

Adult↗