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Biomedical subjects

D K Luscombe

Publications and source records attributed to D K Luscombe.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers.

Administration, Oral↗
PubMed1992

A survey of prescription label preferences among community pharmacy patrons.

Fifty-five randomly selected community pharmacy patrons were surveyed regarding their preferences between four different prescription labels. The variables displayed on the four labels were: (i) laser printed, (ii) dot-matrix printed, (iii) glossy surface, and (iv) matt surface. The study population was stratified by age and gender. Statistical analysis of the results indicated a clear preference by all groups for the laser printed labels (P less than 0.001), and the only other statistically significant finding was the preference for the matt surface (P less than 0.05) of females between the ages of 16 and 39. The implications for these differences on label readability are discussed, and recommendations are offered for the use of improved laser technology for computer-generated prescription labels.

Adolescent↗
PubMed1979

Quantitative structure--activity relationships and carminative activity II: steric considerations.

The unexplained variation in the relationships between carminative activities and octanol--water distribution coefficients of various classes of compounds was explained. The steric substituent constant (Es) value, van der Waals volume, and molecular connectivity were introduced into a previously derived correlation. Each parameter brought about an improvement, and molecular connectivity was the most successful. Correlations containing molecular connectivity was the most successful. Correlations containing molecular connectivity terms explained the excess variation. The results were in agreement with a mechanism in which carminative activity depended on the availability of the oxygen atom in the functional group of the molecule and was reduced when the substituent attached to the oxygen hindered the interaction between the oxygen atom and the receptor.

Animals↗
PubMed1979

Studies on the absorption, distribution and elimination of 6-o-chlorophenyl-2,4-dihydro-2(N-methyl-piperazin-1-yl)-methylene-8-nitro-1H-imidazo[1,2-a] [1,4]benzodiazepin-1-one methanesulphonate in the male rat and rabbit.

The fate of a novel imidazo-benzodiazepine (I) was studied in male rats and rabbits using 14C and 3H-labelled I. In both species the compound was rapidly and widely absorbed after an oral dose of 5 mg/kg to give peak tissue and plasma levels after 1 hour in the rat and 4 hours in the rabbit. The highest concentrations of radioactivity were present in the liver (rat) and liver, kidney and subcutaneous fat (rabbit). Plasma levels of radioactivity fell to 3% of the maximum value in 24 hours in the rat but 48 hours were required for a similar fall in the rabbit. The main route of elimination of radioactivity was via the bile followed by excretion in the faeces. For the rat the rate of biliary elimination was 16.6% of the administered dose/hour; for the rabbit this rate was 5.6%/hour. Recovery of administered radioactivity during 0-24 hours for urine and faeces respectively was 4.8% and 69% for the rat and 23.2% and 10.9% for the rabbit. Up to 97% of the radioactivity administered to rats could be recovered in the excreta in the 7 days following dosing. Up to 90% of the dose administered to rabbits appeared in the excreta during 10 days. No unchanged (I) could be detected in the urine or bile. The radioactive metabolites were polar products, some of which were in the form of glucuronide conjugates.

Animals↗
PubMed1979

Metabolism of beclamide, N-benzyl-3-chloropropionamide, in man.

1. Following oral administration of [14C]beclamide to human subjects there was almost complete elimination of radioactivity in the urine within 48 h. 2. Less than 1% of the administered dose was excreted unchanged. 3. The major metabolites were (a) N-(4-hydroxybenzyl)-3-chloropropionamide, (4-hydroxybeclamide; c. 56%), which was eliminated to a small extent in the free form and as a sulphate but mainly as a glucuronide, and (b) hippuric acid (c. 20%). 4. Six minor metabolites were also detected, of which the following were identified: benzoic acid (up to c. 7%), N-(4-hydroxybenzyl-3-chloro-2-hydroxypropionamide, (dihydroxy-beclamide; c. 2%, mostly as a glucuronide) and 4-hydroxybenzoic acid (c. 0.6%, partly as a glucuronide).

Adult↗
PubMed1978

Quantitative structure-activity relationships and carminative activity.

Carminative activities of 34 alcohols, esters, ethers, phenols, and carbonyl compounds were determined using the guinea pig isolated ileum preparation and are expressed as the ability to produce a 50% inhibition (ID50) of a standard response to carbachol. Aqueous solubilities were measured at 37 degrees using either UV absorption or GLC. The ratios of solubility to ID50 were reasonably constant, suggesting nonspecific biological activity, similar to that previously observed with general anesthetics. Hansch analysis indicated that carminative activities were largely controlled by solubility, as indicated by octanol-water distribution coefficients. The principal remaining factor appeared to be the steric availability of the oxygen atom in the functional group of the compound.

Animals↗
PubMed1977

Efficacy, side-effects, plasma and blood levels of maprotiline (Ludiomil).

Two trials of maprotiline (Ludiomil) were performed in general practice. In the first study depressed patients were given either 75 mg of maprotiline in a single dose or 25 mg three times daily. Assessments of the severity of depression and of side-effects were made initially and following 1, 2 and 4 weeks' treatment. At each assessment measurements of plasma levels of maprotiline were made. A second trial was performed in which some patients receiving 75 mg single dose of maprotiline had whole blood levels of maprotiline assayed. Steady-state levels of maprotiline were achieved after one week but these levels showed considerable individual variability. No clear correlation emerged between clinical response, side-effects and plasma or blood levels. Some of the factors which may be responsible are discussed.

Adult↗
PubMed1977

Pharmacokinetic studies in obsessional patients.

As part of a larger controlled study, 9 patients with chronic obsessive-compulsive rituals received oral clomipramine (Anafranil, Geigy Pharmaceuticals) and behavioural treatment. Dosage was 20 mg clomipramine during the first three days of treatment, increasing gradually over the next few weeks to a maximum daily dose of 200 mg clomipramine unless side-effects dictated a lower dose. Blood was sampled at weekly intervals and the plasma fraction analyzed simultaneously for clomipramine and its primary metabolic breakdown product, N-desmethylclomipramine, using a double radioisotope derivative technique. Plasma concentrations of clomipramine and desmethylclomipramine were observed to rise as the administered dose was increased during the first few weeks of treatment. However, within seven to fourteen days of constant daily dosing steady-state levels were reached in the plasma of clomipramine and its metabolite. Higher plasma levels were found with higher doses. Steady plasma clomipramine levels appeared to be related to dosage, the mean steady-state plasma concentrations between weeks 5 and 11 of treatment being 99 ng/ml, 145 ng/ml and 180 ng/ml, in patients receiving daily doses of 100, 150 and 200 mg clomipramine, respectively. In contrast, plasma metabolite levels did not show any apparent relationship to dosage. In most patients, the concentration of desmethylchlomipramine in the plasma was approximately twice that of the parent compound.

Adolescent↗
PubMed1977

A clinical trial of a 50 mg formulation of clomipramine (Anafranil) with steady-state plasma level measurements.

Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.

Adult↗
PubMed1977

Factors influencing plasma drug concentrations.

The usefulness of measuring plasma concentrations of drugs in patients is now well established and permits a greater efficacy and safety of treatment since dosage can be adjusted on an individual basis. In monitoring plasma concentrations one must recognize that a number of factors may influence these levels. For instance, levels may be affected by age, body-weight and size, genetical factors, abnormalities of water and electrolyte balance and complications associated with pathological conditions such as renal and hepatic impairment. Likewise, plasma levels will depend on dosage, time and route of drug administration, the bioavailability of the drug and time of blood sampling. In addition, absorption, distribution, metabolism, excretion and concurrent drug administration may profoundly affect plasma drug concentrations.

Age Factors↗
PubMed1977

Plasma level studies with clomipramine (anafranil)

Patients showing symptoms of depressive illness were treated in general practice with one of four clomipramine (Anafranil) dosage regimes (25 mg t.d.s., 75 mg o.n., 10 mg t.d.s. and 30 mg o.n.). Blood was sampled on admission to the study and at days 7, 14 and 28. Plasma analysis revealed that steady-state concentrations of clomipramine and its main metabolite desmethyclomipramine were reached at day 7 of treatment in each of the dosage groups. No apparent relationship between dosage and plasma level of clomipramine was found in this study since there was no significant difference between mean steady-state plasma levels in each of the four dosage regimes. In contrast, plasma concentrations of desmethylclomipramine appeared to be directly related to the dose of clomipramine administered. Intersubject variations in plasma levels of the parent compound within each dosage group ranged from three to fourteen-fold.

Adult↗
PubMed1976

Preliminary studies on the absorption, distribution and excretion of N-(2-hydroxyethyl)-maleopimarimidyl morpholide (3H-RU 18492) in the female rat and dog.

Following the oral administration of 3H-labelled N-(2-hydroxyethyl)-maleopimarimidyl morpholide (3H-RU 18 492) to rats and dogs, radioactivity was detected in plasma and the various tissues examined. However, the major fraction of the dose remained unabsorbed and the highest concentrations of radioactivity were found in the liver. In both species the major route of excretion of radioactivity was via the bile.

Animals↗