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Biomedical subjects

J D Price

Publications and source records attributed to J D Price.

At least 19 recordsLinked to original sources
PubMed1990

Stereoselective pharmacokinetics of tocainide in human uraemic patients and in healthy subjects.

The disposition of tocainide enantiomers were examined in healthy human subjects and uraemic patients following a single i.v. dose (200 mg) of racemic tocainide hydrochloride. In the healthy subjects, the total body clearance of R(-)-tocainide was significantly greater than that of S(+)-tocainide (2.62 vs 1.70 ml.min-1.kg-1). Renal clearance also favoured R(-)-tocainide and appeared to contribute significantly to the stereoselective total body clearance. The volume of distribution of the enantiomers did not differ significantly. Uraemia produced a marked decrease in the total body clearance with no apparent effect on the volume of distribution of both enantiomers. The S/R ratio for total body clearance decreased significantly from 0.66 in healthy subjects to 0.54 in the uraemics, while the ratio for terminal elimination half-life significantly increased from 1.43 to 1.59. These results indicate that uraemia alters the degree of stereoselectivity in the pharmacokinetic parameters of tocainide enantiomers.

Adult↗
PubMed1989

In vitro protein binding of propafenone in normal and uraemic human sera.

The protein binding of propafenone, a Class I antiarrhythmic agent, was studied in vitro using a selective and sensitive electron-capture detection gas-liquid capillary chromatographic assay method developed in our laboratory. The concentration-dependency of the serum protein binding of propafenone was confirmed in vitro by equilibrium dialysis, using serum obtained from healthy human subjects and patients with chronic renal failure. In normal serum the unbound fraction of propafenone was 0.027 at a propafenone concentration of 0.25 microgram.ml-1, 0.041 within the therapeutic concentration range (0.5-2 micrograms.ml-1), 0.138 at a propafenone concentration of 25 micrograms.ml-1, and 0.187 when the propafenone concentration was increased to 100 micrograms.ml-1. There was no evidence of significant concentration-dependent changes in unbound fraction within the propafenone concentration range of 0.5-1.5 micrograms.ml-1. However, concentration-dependent binding was demonstrated at concentrations greater than 1.5 micrograms.ml-1. A high-affinity, low-capacity binding site (K1 = 6.53 x 10(5) l.mol-1; n1P1 = 1.73 x 10(-4) mol.l-1) and a low-affinity, high-capacity binding site (K2 = 8.77 x 10(3) l.mol-1; n2P2 = 8.57 x 10(-3) mol. x l-1) were identified. In pooled uraemic serum the unbound fraction of propafenone was approximately 50% of that of normal serum throughout the concentration range studied (1-5 micrograms.ml-1). In sera from patients with chronic renal failure the increase in propafenone binding ratio or the decrease in unbound fraction was associated with the increase in alpha 1-acid glycoprotein concentrations, and there was a correlation (r = 0.8302) between alpha 1-acid glycoprotein concentration and the propafenone binding ratio.

Adult↗
PubMed1989

Biopsychosocial aspects of long-term survival on end-stage renal failure therapy.

At ten-years follow-up of 64 haemodialysis patients, 43 had died and 21 were alive, twelve with cadaver renal transplants and nine on haemodialysis. Examination of the influence of psychological, demographic, physical and biochemical factors revealed the Beck Depression Inventory and age as the two most important predictors of survival. The behaviour of the patient was directly responsible for five (11.6%) of the deaths, by suicide in three cases and dietary non-compliance in two cases. Hypothetical mechanisms linking depression with reduced survival have been reviewed. As the impact of depression on survival was maximal in the first few years of dialysis, monitoring for depression should be incorporated into routine care from the start of dialysis together with evaluative interventions that might enhance survival.

Adolescent↗
PubMed1988

Linearity of metoclopramide kinetics at doses of 5-20 mg.

The disposition of metoclopramide was studied on a four-way crossover basis in six healthy non-smoking volunteers. The linearity of kinetic parameters and absolute bioavailability of metoclopramide were examined. In contrast to previous reports, metoclopramide obeyed linear kinetics over oral doses ranging from 5 to 20 mg. The absolute bioavailability of metoclopramide was 0.76 +/- 0.38 (mean +/- s.d.) from the oral dosage forms examined in this study.

Biological Availability↗
PubMed1988

Effect of haemodialysis on metoclopramide kinetics in patients with severe renal failure.

The kinetics of metoclopramide and the effects of haemodialysis on metoclopramide kinetics were examined in eight uraemic subjects 1 h and 24 h prior to the onset of dialysis. In spite of the relatively minor contribution of renal clearance to total body clearance in normals, metoclopramide kinetics were substantially altered in uraemia. The total body clearance was decreased by 2-4 fold, terminal elimination half-life proportionately increased, while the volume of distribution appeared to be unaffected compared with that previously demonstrated in normal healthy subjects. Haemodialysis does not appear to be effective in removing metoclopramide from the body and metoclopramide clearance subsequent to dialysis is unaltered. The kinetic parameters in the uraemic subjects are not significantly different between drug administrations 1 or 24 h prior to the time of onset of haemodialysis. Following kidney transplantation, in one subject, there appeared to be a rapid return to apparently normal kinetics from the uraemic state.

Female↗
PubMed1987

Ion-exchange resins as potential phosphate-binding agents for renal failure patients: effect of the physicochemical properties of resins on phosphate and bile salt binding.

The effect of resin type, degree of cross-linking, bead size, and surface area on the phosphate and bile salt binding characteristics of five strongly basic Dowex anion-exchange resins in the chloride form was studied. The maximum uptake of phosphate (expressed as uptake of phosphorus) from sodium phosphate solutions was 137, 82, 86, 138, and 76 mg of phosphorus per gram of dry Dowex resins XF 43311, XY 40013, XF 43254, XY 40011, and XY 40012, respectively. The presence of simulated gastric or intestinal fluids resulted in small but insignificant alterations in phosphorus uptake by the resins. The resins all bound similar amounts of phosphorus and taurocholate (80-100% of the total phosphorus and taurocholate in solution) at physiological concentrations of phosphate and bile salt. Dowex resins XY 40013 and XF 43254, with identical physicochemical properties, but different bead sizes and surface areas, bound similar amounts of the bile salt sodium taurocholate at all taurocholate concentrations, indicating that binding was not restricted to the surface sites on the resin bead. The 2% cross-linked resins bound 3-4 times more taurocholate than the 8% cross-linked resins (at high taurocholate concentrations); the smaller pore size of the latter resins probably presents a greater mechanical exclusion barrier than the larger pore size of the 2% cross-linked resins.

Anions↗
PubMed1985

Candida glabrata (syn. Torulopsis glabrata) associated with a chronic hyperplastic lesion of the palate.

A case initially presenting as chronic hyperplastic candidosis is described. After treatment with nystatin on three separate occasions over a seven-year period, a lesion similar to that diagnosed originally occurred in the same site. Further examination of this later occurrence showed it to be associated with the imperfect fungus Candida glabrata which had a high minimum inhibitory concentration for nystatin (greater than 30 micrograms/ml). The lesion eventually resolved following treatment with miconazole gel and surgical excision of the hyperplastic tissue. The patient has remained symptomless for a two-year follow-up period.

Adult↗
PubMed1985

Brain gamma-aminobutyric acid deficiency in dialysis encephalopathy.

We measured levels of gamma-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50% in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35%) in cerebral cortex of the dialysis encephalopathy patients.

Adult↗
PubMed1984

Nonlinear bioavailability of metoclopramide in the rat: evidence for saturable first-pass metabolism.

In vivo and in vitro experiments were conducted in rats to examine the possibility of either extrahepatic metabolism or saturable first-pass effect as an explanation for the unusual presystemic clearance of metoclopramide (I) previously reported. In vivo studies involved two-thirds hepatectomized rats and animals pretreated with carbon tetrachloride to induce hepatic necrosis, whereas in vitro studies involved incubation of equal amounts of I (5.0 mumol/mL) with various tissue homogenates (viz., liver, kidney, and lung) or their 9000 X g supernatant fractions. Results suggest that the metabolism of I principally occurs in the rat liver, and there was no evidence suggesting the involvement of kidney or lung tissue in the metabolism of I. Forty-eight-hour cumulative urinary excretion studies following oral and intravenous administration of less than or equal to 5.0 mg/kg of metoclopramide hydrochloride were conducted. The bioavailability (F) values of I at dosage levels 0.1, 0.5, 1.0, and 5.0 mg/kg were 0.49, 0.75, 0.77, and 0.83, respectively. It is concluded that the liver is the primary organ for the metabolism of I in the rat and that the drug exhibits dose-dependent hepatic first-pass metabolism.

Animals↗
PubMed1984

Complications of surgery for oral malignancy.

The post-operative complications on 100 patients who had surgery for oral malignancy were studied. Sixty-five per cent developed one or more complications, wound breakdown being the most common. Complications increased with the clinical staging of the tumour and the extent of the surgery, but were not significantly related to age (if under 80 years), site or whether radiotherapy had been previously employed.

Adult↗